Biology and ecology of pharmaceutical marine molluscs 9780815354246, 081535424X, 9781351133388, 9781351133371, 9781351133364

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Content: Chapter 1. Introduction. Chapter 2 Marine Molluscs: Biology and Pharmaceutical aspects. References. Compounds. Index.

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Biology and Ecology of Pharmaceutical Marine Mollusks

Biology and Ecology of Pharmaceutical Marine Life Book Series  Series Lead Author Ramasamy Santhanam,Ph.D  Former Dean, Fisheries College and Research Institute Tamil Nadu Veterinary and Animal Sciences University (presently Tamil Nadu Dr.J.Jayalalithaa Fisheries University) Thoothukudi 628 008, India Email: [email protected]; [email protected]

Books in the Series:  Biology and Ecology of Pharmaceutical Marine Plants  Biology and Ecology of Pharmaceutical Marine Sponges  Biology and Ecology of Pharmaceutical Marine Mollusks 

Biology and Ecology of Pharmaceutical Marine Mollusks

By

Ramasamy Santhanam, Manavalan Gobinath, and Santhanam Ramesh

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 ©  2019 by Taylor & Francis Group, LLC   CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-0-8153-5424-6 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice:  Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging‑ in‑ P ublication Data  Names: Santhanam, Ramasamy, 1946- author. | Gobinath, Manavalan, author. | Ramesh, Santhanam, 1979- author. Title: Biology and ecology of pharmaceutical marine mollusks / authors: Ramasamy Santhanam, Manavalan Gobinath, and Santhanam Ramesh. Description: Boca Raton : Taylor & Francis, 2019. | Includes bibliographical references and index. Identifiers: LCCN 2018034911| ISBN 9780815354246 (hardback : alk. paper) | ISBN 9781351133388 (pdf) | ISBN 9781351133371 (epub) | ISBN 9781351133364 (mobi/kindle) Subjects: LCSH: Mollusks. | Mollusks--Therapeutic use. | Marine natural products. Classification: LCC QL408 .S36 2019 | DDC 594--dc23 LC record available at https://lccn.loc.gov/2018034911 Visit the Taylor & Francis Web site at  http://www.taylorandfrancis.com  and the CRC Press Web site at  http://www.crcpress.com 

Contents Preface........................................................................................................................................................................................xxi Authors......................................................................................................................................................................................xxiii Chapter 1 Introduction.............................................................................................................................................................. 1 Pharmaceutical Marine Mollusks............................................................................................................................. 1 Chapter 2 Marine Mollusks: Biology and Pharmaceutical Aspects......................................................................................... 3 2.1 Class: Bivalvia............................................................................................................................................... 3 Anadara broughtonii (Schrenck, 1867) (=Arca inflata; Scapharca broughtonii)......................................... 3 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 3 Compound(s) and Activities............................................................................................................. 3 Anadara kagochimensis (Tokunaga, 1906) (=Scapharca subcrenata; Arca kagoshimensis)........................ 3 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 4 Compound(s) and Activities............................................................................................................. 4 Anadara antiquata (Linnaeus, 1758)............................................................................................................ 4 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 4 Compound(s) and Activities............................................................................................................. 4 Anadara satowi (Dunker, 1882).................................................................................................................... 4 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 5 Compound(s) and Activities............................................................................................................. 5 Tegillarca granosa (Linnaeus, 1758) (=Arca granosa)................................................................................. 5 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 5 Compound(s) and Activities............................................................................................................. 5 Tegillarca rhombea (Born, 1778) (=Anadara rhombea)............................................................................... 6 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 6 Compound(s) and Activities............................................................................................................. 6 Cerastoderma edule (Linnaeus, 1758).......................................................................................................... 6 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 6 Compound(s) and Activities............................................................................................................. 6 Tridacna maxima (Röding, 1798).................................................................................................................. 6 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 7 Compound(s) and Activities............................................................................................................. 7 Tridacna sp.................................................................................................................................................... 7 Compound(s) and Activities............................................................................................................. 7 Galatea paradoxa (Born, 1778).................................................................................................................... 7 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 7 Compound(s) and Activities............................................................................................................. 7 Pholas orientalis (Gmelin, 1791).................................................................................................................. 7 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 8 Compound(s) and Activities............................................................................................................. 8 Mya arenaria (Linnaeus, 1758)..................................................................................................................... 8 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 8 Compound(s) and Activities............................................................................................................. 9 Mytilus chilensis (Hupé, 1854) (=Mytilus edulis chilensis).......................................................................... 9 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 9 Compound(s) and Activities............................................................................................................. 9 Mytilus edulis (Linnaeus, 1758).................................................................................................................... 9 Biology�������������������������������������������������������������������������������������������������������������������������������������������� 9 Compound(s) and Activities........................................................................................................... 10

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Mytilus galloprovincialis (Lamarck, 1819)................................................................................................. 10 Biology������������������������������������������������������������������������������������������������������������������������������������������ 11 Compound(s) and Activities........................................................................................................... 11 Mytilus unguiculatus (Valenciennes, 1858) (=Mytilus coruscus; Mytilus crassitesta)............................... 12 Biology������������������������������������������������������������������������������������������������������������������������������������������ 12 Compound(s) and Activities........................................................................................................... 12 Bathymodiolus thermophilus (Kenk and Wilson, 1985).............................................................................. 12 Biology������������������������������������������������������������������������������������������������������������������������������������������ 13 Compound(s) and Activities........................................................................................................... 13 Crenomytilus grayanus (Dunker, 1853)...................................................................................................... 13 Biology������������������������������������������������������������������������������������������������������������������������������������������ 13 Compound(s) and Activities........................................................................................................... 13 Geukensia demissa (Dillwyn, 1817)............................................................................................................ 14 Biology������������������������������������������������������������������������������������������������������������������������������������������ 14 Compound(s) and Activities........................................................................................................... 14 Lithophaga teres (Philippi, 1846)................................................................................................................ 14 Biology������������������������������������������������������������������������������������������������������������������������������������������ 14 Compound(s) and Activities........................................................................................................... 14 Modiolus (Linnaeus, 1758).......................................................................................................................... 14 Biology������������������������������������������������������������������������������������������������������������������������������������������ 15 Compound(s) and Activities........................................................................................................... 15 Perna canaliculus (Gmelin, 1791)............................................................................................................... 15 Biology������������������������������������������������������������������������������������������������������������������������������������������ 15 Compound(s) and Activities........................................................................................................... 16 Others�������������������������������������������������������������������������������������������������������������������������������������������� 16 Perna viridis (Linnaeus, 1758).................................................................................................................... 16 Biology������������������������������������������������������������������������������������������������������������������������������������������ 16 Compound(s) and Activities........................................................................................................... 17 Crassostrea gigas (Thunberg, 1793)........................................................................................................... 17 Biology������������������������������������������������������������������������������������������������������������������������������������������ 18 Compound(s) and Activities........................................................................................................... 18 Crassostrea madrasensis (Preston, 1916)................................................................................................... 18 Biology������������������������������������������������������������������������������������������������������������������������������������������ 18 Compound(s) and Activities........................................................................................................... 19 Crassostrea rhizophorae (Guilding, 1828).................................................................................................. 19 Biology������������������������������������������������������������������������������������������������������������������������������������������ 19 Compound(s) and Activities........................................................................................................... 19 Crassostrea virginica (Gmelin, 1791)......................................................................................................... 19 Biology������������������������������������������������������������������������������������������������������������������������������������������ 20 Compound(s) and Activities........................................................................................................... 20 Ostrea edulis (Linnaeus, 1758)................................................................................................................... 20 Biology������������������������������������������������������������������������������������������������������������������������������������������ 20 Compound(s) and Activities........................................................................................................... 20 Saccostrea cucullata (Born, 1778).............................................................................................................. 20 Biology������������������������������������������������������������������������������������������������������������������������������������������ 21 Compound(s) and Activities........................................................................................................... 21 Hyotissa sp................................................................................................................................................... 21 Compound(s) and Activities........................................................................................................... 21 Pinctada imbricata fucata (Gould, 1850) (=Pinctada fucata).................................................................... 21 Biology������������������������������������������������������������������������������������������������������������������������������������������ 22 Compound(s) and Activities........................................................................................................... 22 Pinctada imbricata (Roding, 1798)............................................................................................................. 22 Biology������������������������������������������������������������������������������������������������������������������������������������������ 22 Compound(s) and Activities........................................................................................................... 22 Pinctada margaritifera (Linnaeus, 1758) (=Pteria margaritifera)............................................................. 22 Biology������������������������������������������������������������������������������������������������������������������������������������������ 23 Compound(s) and Activities........................................................................................................... 23

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Pteria avicular (Holten, 1802) (=Pteria chinensis).................................................................................... 23 Biology������������������������������������������������������������������������������������������������������������������������������������������ 23 Compound(s) and Activities........................................................................................................... 23 Pteria penguin (Röding, 1798).................................................................................................................... 23 Biology������������������������������������������������������������������������������������������������������������������������������������������ 24 Compound(s) and Activities........................................................................................................... 24 Nodipecten nodosus (Linnaeus, 1758)........................................................................................................ 24 Biology������������������������������������������������������������������������������������������������������������������������������������������ 24 Compound(s) and Activities........................................................................................................... 24 Minnivola pyxidata (Born, 1778)................................................................................................................ 25 Biology������������������������������������������������������������������������������������������������������������������������������������������ 25 Compound(s) and Activities........................................................................................................... 25 Argopecten ventricosus (Sowerby II, 1842)................................................................................................ 26 Biology������������������������������������������������������������������������������������������������������������������������������������������ 26 Compound(s) and Activities........................................................................................................... 26 Amusium pleuronectes (Linnaeus, 1758)..................................................................................................... 26 Biology������������������������������������������������������������������������������������������������������������������������������������������ 27 Compound(s) and Activities........................................................................................................... 27 Azumapecten farreri (Jones and Preston, 1904) (=Chlamys farreri).......................................................... 27 Biology������������������������������������������������������������������������������������������������������������������������������������������ 27 Compound(s) and Activities........................................................................................................... 27 Spondylus varius (Sowerby, 1829).............................................................................................................. 27 Biology������������������������������������������������������������������������������������������������������������������������������������������ 28 Compound(s) and Activities........................................................................................................... 28 Corbicula japonica (Prime, 1864)............................................................................................................... 28 Biology������������������������������������������������������������������������������������������������������������������������������������������ 28 Compound(s) and Activities........................................................................................................... 28 Donax cuneatus (Linnaeus, 1758)............................................................................................................... 28 Biology������������������������������������������������������������������������������������������������������������������������������������������ 28 Compound(s) and Activities........................................................................................................... 29 Donax faba (Gmelin, 1791)......................................................................................................................... 29 Biology������������������������������������������������������������������������������������������������������������������������������������������ 29 Compound(s) and Activities........................................................................................................... 29 Donax incarnatus (Gmelin, 1791)............................................................................................................... 29 Biology������������������������������������������������������������������������������������������������������������������������������������������ 30 Compound(s) and Activities........................................................................................................... 30 Donax scortum (Linnaeus, 1758)................................................................................................................ 30 Biology������������������������������������������������������������������������������������������������������������������������������������������ 30 Compound(s) and Activities........................................................................................................... 30 Geloina expansa (Mousson, 1849) (=Geloina erosa; Polymesoda erosa).................................................. 30 Biology������������������������������������������������������������������������������������������������������������������������������������������ 31 Compound(s) and Activities........................................................................................................... 31 Villorita cyprinoides (Gray, 1825)............................................................................................................... 31 Biology������������������������������������������������������������������������������������������������������������������������������������������ 31 Compound(s) and Activities........................................................................................................... 31 Mactra quadrangularis (Reeve, 1854) (=Mactra veneriformis)................................................................. 31 Biology������������������������������������������������������������������������������������������������������������������������������������������ 32 Compound(s) and Activities........................................................................................................... 32 Mactromeris polynyma (Stimpson, 1860) (=Spisula polynyma)................................................................. 32 Biology������������������������������������������������������������������������������������������������������������������������������������������ 32 Compound(s) and Activities........................................................................................................... 32 Atactodea striata (Gmelin, 1791)................................................................................................................ 33 Biology������������������������������������������������������������������������������������������������������������������������������������������ 33 Compound(s) and Activities........................................................................................................... 33 Sinonovacula constricta (Lamarck, 1818).................................................................................................. 33 Biology������������������������������������������������������������������������������������������������������������������������������������������ 33 Compound(s) and Activities........................................................................................................... 33

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Anomalocardia flexuosa (Linnaeus, 1767) (=Anomalocardia brasiliana).................................................. 34 Biology������������������������������������������������������������������������������������������������������������������������������������������ 34 Compound(s) and Activities........................................................................................................... 34 Callista chione (Linnaeus, 1758)................................................................................................................ 34 Biology������������������������������������������������������������������������������������������������������������������������������������������ 34 Compound(s) and Activities........................................................................................................... 34 Chionista fluctifraga (Sowerby II, 1853) (=Chione fluctifraga)................................................................. 34 Biology������������������������������������������������������������������������������������������������������������������������������������������ 35 Compound(s) and Activities........................................................................................................... 35 Cyclina sinensis (Gmelin, 1791)................................................................................................................. 35 Biology������������������������������������������������������������������������������������������������������������������������������������������ 35 Compound(s) and Activities........................................................................................................... 35 Gafrarium divaricatum (Gmelin, 1791)...................................................................................................... 35 Biology������������������������������������������������������������������������������������������������������������������������������������������ 36 Compound(s) and Activities........................................................................................................... 36 Marcia opima (Gmelin, 1791)..................................................................................................................... 36 Biology������������������������������������������������������������������������������������������������������������������������������������������ 37 Compound(s) and Activities........................................................................................................... 37 Mercenaria campechiensis (Gmelin, 1791)................................................................................................ 37 Biology������������������������������������������������������������������������������������������������������������������������������������������ 37 Compound(s) and Activities........................................................................................................... 37 Mercenaria mercenaria (Linnaeus, 1758)................................................................................................... 37 Biology������������������������������������������������������������������������������������������������������������������������������������������ 38 Compound(s) and Activities........................................................................................................... 38 Meretrix casta (Chemnitz, 1782)................................................................................................................. 38 Biology������������������������������������������������������������������������������������������������������������������������������������������ 38 Compound(s) and Activities........................................................................................................... 38 Meretrix lusoria (Roeding, 1798)................................................................................................................ 39 Biology������������������������������������������������������������������������������������������������������������������������������������������ 39 Compound(s) and Activities........................................................................................................... 39 Meretrix meretrix (Linnaeus, 1758)............................................................................................................. 39 Biology������������������������������������������������������������������������������������������������������������������������������������������ 39 Compound(s) and Activities........................................................................................................... 40 Meretrix petechialis (Lamarck, 1818)......................................................................................................... 40 Biology������������������������������������������������������������������������������������������������������������������������������������������ 40 Compound(s) and Activities........................................................................................................... 40 Paratapes undulatus (Born, 1778)............................................................................................................... 41 Biology������������������������������������������������������������������������������������������������������������������������������������������ 41 Compound(s) and Activities........................................................................................................... 41 Protapes gallus (Gmelin, 1791).................................................................................................................. 41 Biology������������������������������������������������������������������������������������������������������������������������������������������ 41 Compound(s) and Activities........................................................................................................... 41 Ruditapes decussatus (Linnaeus, 1758)...................................................................................................... 42 Biology������������������������������������������������������������������������������������������������������������������������������������������ 42 Compound(s) and Activities........................................................................................................... 42 Ruditapes philippinarum (Adams and Reeve, 1850) (=Tapes (Ruditapes) philippinarum)........................ 42 Biology������������������������������������������������������������������������������������������������������������������������������������������ 42 Compound(s) and Activities........................................................................................................... 43 Sunetta scripta (Linnaeus, 1758)................................................................................................................. 43 Biology������������������������������������������������������������������������������������������������������������������������������������������ 44 Compound(s) and Activities........................................................................................................... 44 Tivela mactroides (Born, 1778)................................................................................................................... 44 Biology������������������������������������������������������������������������������������������������������������������������������������������ 44 Compound(s) and Activities........................................................................................................... 44 2.2 Class: Gastropoda........................................................................................................................................ 44 Cellana grata (Gould, 1859)....................................................................................................................... 44

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Biology������������������������������������������������������������������������������������������������������������������������������������������ 44 Compound(s) and Activities........................................................................................................... 44 Cellana radiata (Born, 1778)..................................................................................................................... 45 Biology������������������������������������������������������������������������������������������������������������������������������������������ 45 Compound(s) and Activities........................................................................................................... 45 Cellana toreuma (Reeve, 1854)................................................................................................................... 45 Biology������������������������������������������������������������������������������������������������������������������������������������������ 45 Compound(s) and Activities........................................................................................................... 45 Patella rustica (Linnaeus, 1758)................................................................................................................. 45 Biology������������������������������������������������������������������������������������������������������������������������������������������ 45 Compound(s) and Activities........................................................................................................... 46 Patella vulgata (Linné, 1758)...................................................................................................................... 46 Biology������������������������������������������������������������������������������������������������������������������������������������������ 46 Compound(s) and Activities........................................................................................................... 46 Fissurella cumingi (Reeve, 1849)................................................................................................................ 46 Compound(s) and Activities........................................................................................................... 46 Fissurella latimarginata (Sowerby I, 1835)................................................................................................ 47 Compound(s) and Activities........................................................................................................... 47 Fissurella maxima (Sowerby I, 1834)......................................................................................................... 47 Compound(s) and Activities........................................................................................................... 47 Megathura crenulata (Sowerby I, 1825)..................................................................................................... 47 Biology������������������������������������������������������������������������������������������������������������������������������������������ 47 Compound(s) and Activities........................................................................................................... 48 Haliotis discus discus (Reeve, 1846)........................................................................................................... 48 Biology������������������������������������������������������������������������������������������������������������������������������������������ 48 Compound(s) and Activities........................................................................................................... 48 Haliotis discus hannai (Ino, 1953).............................................................................................................. 48 Biology������������������������������������������������������������������������������������������������������������������������������������������ 48 Compound(s) and Activities........................................................................................................... 48 Haliotis diversicolor (Reeve, 1846)............................................................................................................ 49 Biology������������������������������������������������������������������������������������������������������������������������������������������ 49 Compound(s) and Activities........................................................................................................... 50 Haliotis laevigata (Donovan, 1808)............................................................................................................ 50 Biology������������������������������������������������������������������������������������������������������������������������������������������ 50 Compound(s) and Activities........................................................................................................... 50 Haliotis rubra (Leach, 1814)....................................................................................................................... 50 Biology������������������������������������������������������������������������������������������������������������������������������������������ 50 Compound(s) and Activities........................................................................................................... 51 Haliotis rufescens (Swainson, 1822)........................................................................................................... 51 Biology������������������������������������������������������������������������������������������������������������������������������������������ 51 Compound(s) and Activities........................................................................................................... 51 Siphonaria diemensis (Quoy and Gaimard, 1833)...................................................................................... 51 Biology������������������������������������������������������������������������������������������������������������������������������������������ 51 Compound(s) and Activities........................................................................................................... 52 Trimusculus costatus (Krauss, 1848)........................................................................................................... 52 Biology������������������������������������������������������������������������������������������������������������������������������������������ 52 Compound(s) and Activities........................................................................................................... 52 Trimusculus peruvianus (Sowerby I, 1835)................................................................................................. 53 Compound(s) and Activities........................................................................................................... 53 Turritella acutangula (Linnaeus, 1758) (=Turritella duplicata)................................................................. 53 Biology������������������������������������������������������������������������������������������������������������������������������������������ 54 Compound(s) and Activities........................................................................................................... 54 Turritella attenuata (Reeve, 1849).............................................................................................................. 54 Biology������������������������������������������������������������������������������������������������������������������������������������������ 54 Compound(s) and Activities........................................................................................................... 54

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Planaxis sulcatus (Born, 1791)................................................................................................................... 54 Biology������������������������������������������������������������������������������������������������������������������������������������������ 54 Compound(s) and Activities........................................................................................................... 54 Euthria cornea (Linnaeus, 1758) (=Buccinulum corneum)........................................................................ 55 Biology������������������������������������������������������������������������������������������������������������������������������������������ 55 Compound(s) and Activities........................................................................................................... 55 Cerithidea cingulata (Gmelin, 1791).......................................................................................................... 55 Biology������������������������������������������������������������������������������������������������������������������������������������������ 55 Compound(s) and Activities........................................................................................................... 55 Cerithidea obtusa (Lamarck, 1822)............................................................................................................ 56 Biology������������������������������������������������������������������������������������������������������������������������������������������ 56 Compound(s) and Activities........................................................................................................... 56 Telescopium telescopium (Linnaeus, 1758)................................................................................................. 56 Biology������������������������������������������������������������������������������������������������������������������������������������������ 56 Compound(s) and Activities........................................................................................................... 57 Scaphander lignarius (Linnaeus, 1767)...................................................................................................... 57 Biology������������������������������������������������������������������������������������������������������������������������������������������ 57 Compound(s) and Activities........................................................................................................... 57 Smaragdinella calyculata (Broderip and Sowerby, 1829).......................................................................... 58 Biology������������������������������������������������������������������������������������������������������������������������������������������ 58 Compound(s) and Activities........................................................................................................... 58 Bulla striata (Bruguiere, 1792)................................................................................................................... 58 Biology������������������������������������������������������������������������������������������������������������������������������������������ 59 Compound(s) and Activities........................................................................................................... 59 Bulla gouldiana (Pilsbry, 1895).................................................................................................................. 59 Biology������������������������������������������������������������������������������������������������������������������������������������������ 59 Compound(s) and Activities........................................................................................................... 59 Bullacta exarata (Philippi, 1849)................................................................................................................ 59 Biology������������������������������������������������������������������������������������������������������������������������������������������ 60 Compound(s) and Activities........................................................................................................... 60 Navanax inermis (Cooper, 1863)................................................................................................................. 60 Biology������������������������������������������������������������������������������������������������������������������������������������������ 60 Compound(s) and Activities........................................................................................................... 60 Nembrotha sp............................................................................................................................................... 61 Compound(s) and Activities........................................................................................................... 61 Philinopsis depicta (Renier, 1807) (=Aglaja depicta)................................................................................. 61 Biology������������������������������������������������������������������������������������������������������������������������������������������ 61 Compound(s) and Activities........................................................................................................... 61 Philinopsis speciosa (Pease, 1860).............................................................................................................. 62 Biology������������������������������������������������������������������������������������������������������������������������������������������ 62 Compound(s) and Activities........................................................................................................... 62 Bufonaria crumena (Lamarck, 1816).......................................................................................................... 63 Biology������������������������������������������������������������������������������������������������������������������������������������������ 63 Compound(s) and Activities........................................................................................................... 63 Bufonaria echinata (Link, 1807) (=Bursa spinosa).................................................................................... 63 Biology������������������������������������������������������������������������������������������������������������������������������������������ 63 Compound(s) and Activities........................................................................................................... 64 Bufonaria rana (Linnaeus, 1758) (=Bursa rana)........................................................................................ 64 Biology������������������������������������������������������������������������������������������������������������������������������������������ 64 Compound(s) and Activities........................................................................................................... 64 Charonia lampas (Linnaeus, 1758)............................................................................................................. 64 Biology������������������������������������������������������������������������������������������������������������������������������������������ 64 Compound(s) and Activities........................................................................................................... 64 Crepidula fornicata (Linné, 1758).............................................................................................................. 65 Biology������������������������������������������������������������������������������������������������������������������������������������������ 65 Compound(s) and Activities........................................................................................................... 65

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Erronea errones (Linnaeus, 1758) (=Cypraea errones).............................................................................. 65 Biology������������������������������������������������������������������������������������������������������������������������������������������ 65 Compound(s) and Activities........................................................................................................... 65 Cypraea tigris (Linnaeus, 1758).................................................................................................................. 65 Biology������������������������������������������������������������������������������������������������������������������������������������������ 66 Compound(s) and Activities........................................................................................................... 66 Mauritia arabica (Linnaeus, 1758) (=Cypraea arabica)............................................................................ 66 Biology������������������������������������������������������������������������������������������������������������������������������������������ 66 Compound(s) and Activities........................................................................................................... 66 Monetaria moneta (Linnaeus, 1758) (=Cypraea moneta)........................................................................... 66 Biology������������������������������������������������������������������������������������������������������������������������������������������ 67 Compound(s) and Activities........................................................................................................... 67 Ficus ficus (Linnaeus, 1758)........................................................................................................................ 67 Biology������������������������������������������������������������������������������������������������������������������������������������������ 67 Compound(s) and Activities........................................................................................................... 67 Lobatus gigas (Linnaeus, 1758) (=Strombus gigas).................................................................................... 68 Biology������������������������������������������������������������������������������������������������������������������������������������������ 68 Compound(s) and Activities........................................................................................................... 68 Margistrombus marginatus (Linnaeus, 1758) (=Strombus marginatus)...................................................... 68 Biology������������������������������������������������������������������������������������������������������������������������������������������ 68 Compound(s) and Activities........................................................................................................... 68 Harpago chiragra (Linnaeus, 1758) (=Lambis chiragra)........................................................................... 69 Biology������������������������������������������������������������������������������������������������������������������������������������������ 69 Compound(s) and Activities........................................................................................................... 69 Lambis lambis (Linnaeus, 1758)................................................................................................................. 69 Biology������������������������������������������������������������������������������������������������������������������������������������������ 69 Compound(s) and Activities........................................................................................................... 69 Tibia curta (Sowerby II, 1842).................................................................................................................... 70 Biology������������������������������������������������������������������������������������������������������������������������������������������ 70 Compound(s) and Activities........................................................................................................... 70 Coriocella nigra (Blainville, 1824) (=Chelyonotus semperi)...................................................................... 70 Biology������������������������������������������������������������������������������������������������������������������������������������������ 70 Compound(s) and Activities........................................................................................................... 70 Lamellaria sp............................................................................................................................................... 71 Biology������������������������������������������������������������������������������������������������������������������������������������������ 71 Compound(s) and Activities........................................................................................................... 71 Littorina littorea (Linnaeus, 1758) [1]........................................................................................................ 71 Biology������������������������������������������������������������������������������������������������������������������������������������������ 72 Compound(s) and Activities........................................................................................................... 72 Littorina sitkana (Philippi, 1846)................................................................................................................ 72 Biology������������������������������������������������������������������������������������������������������������������������������������������ 72 Compound(s) and Activities........................................................................................................... 72 Phalium glaucum (Linnaeus, 1758)............................................................................................................ 72 Biology������������������������������������������������������������������������������������������������������������������������������������������ 73 Compound(s) and Activities........................................................................................................... 73 Xenophora mekranensis (Newton, 1905).................................................................................................... 73 Biology������������������������������������������������������������������������������������������������������������������������������������������ 73 Compound(s) and Activities........................................................................................................... 73 Neverita didyma (Röding, 1798) (=Polinices didyma)................................................................................ 74 Biology������������������������������������������������������������������������������������������������������������������������������������������ 74 Compound(s) and Activities........................................................................................................... 74 Volegalea cochlidium (Linnaeus, 1758) (=Hemifusus pugilinus; Pugilina cochlidium)............................. 74 Biology������������������������������������������������������������������������������������������������������������������������������������������ 74 Compound(s) and Activities........................................................................................................... 74 Volegalea cochlidium (Linnaeus, 1758) (=Pugilina cochidium)................................................................. 75 Biology������������������������������������������������������������������������������������������������������������������������������������������ 75 Compound(s) and Activities........................................................................................................... 75

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Unedogemmula indica (Röding, 1798) (=Lophiotoma indica)................................................................... 76 Biology������������������������������������������������������������������������������������������������������������������������������������������ 76 Compound(s) and Activities........................................................................................................... 76 Turbinella pyrum (Linnaeus, 1758) (=Xancus pyrum)................................................................................ 76 Biology������������������������������������������������������������������������������������������������������������������������������������������ 76 Compound(s) and Activities........................................................................................................... 76 Agnewia tritoniformis (Blainville, 1832)..................................................................................................... 77 Biology������������������������������������������������������������������������������������������������������������������������������������������ 77 Compound(s) and Activities........................................................................................................... 77 Bedeva paivae (Crosse, 1864)..................................................................................................................... 77 Biology������������������������������������������������������������������������������������������������������������������������������������������ 77 Compound(s) and Activities........................................................................................................... 77 Hexaplex trunculus (Linnaeus, 1758) (=Trunculariopsis trunculus).......................................................... 77 Biology������������������������������������������������������������������������������������������������������������������������������������������ 78 Compound(s) and Activities........................................................................................................... 78 Ocenebra erinaceus (Linnaeus, 1758)......................................................................................................... 78 Biology������������������������������������������������������������������������������������������������������������������������������������������ 79 Compound(s) and Activities........................................................................................................... 79 Murex trapa (Roding, 1798)........................................................................................................................ 79 Biology������������������������������������������������������������������������������������������������������������������������������������������ 79 Compound(s) and Activities........................................................................................................... 79 Murex tribulus (Linnaeus, 1758)................................................................................................................. 80 Biology������������������������������������������������������������������������������������������������������������������������������������������ 80 Compound(s) and Activities........................................................................................................... 80 Tylothais savignyi (Deshayes, 1844) (=Thais savignyi).............................................................................. 80 Biology������������������������������������������������������������������������������������������������������������������������������������������ 80 Compound(s) and Activities........................................................................................................... 80 Stramonita floridana (Conrad, 1837) (=Thais floridana)............................................................................ 80 Biology������������������������������������������������������������������������������������������������������������������������������������������ 81 Compound(s) and Activities........................................................................................................... 81 Semiricinula tissoti (Petit de la Saussaye, 1852) (=Thais tissoti)............................................................... 81 Biology������������������������������������������������������������������������������������������������������������������������������������������ 81 Compound(s) and Activities........................................................................................................... 81 Purpura bufo (Lamarck, 1822) (=Thais bufo)............................................................................................. 82 Biology������������������������������������������������������������������������������������������������������������������������������������������ 82 Compound(s) and Activities........................................................................................................... 82 Purpura persica (Linnaeus, 1758) (=Purpura rudolphi)............................................................................ 82 Biology������������������������������������������������������������������������������������������������������������������������������������������ 83 Compound(s) and Activities........................................................................................................... 83 Rapana bezoar (Linnaeus, 1767)................................................................................................................ 83 Biology������������������������������������������������������������������������������������������������������������������������������������������ 83 Compound(s) and Activities........................................................................................................... 83 Rapana rapiformis (Born, 1778)................................................................................................................. 83 Biology������������������������������������������������������������������������������������������������������������������������������������������ 84 Compound(s) and Activities........................................................................................................... 84 Rapana venosa (Valenciennes, 1846) (=Rapana thomasiana).................................................................... 84 Biology������������������������������������������������������������������������������������������������������������������������������������������ 84 Compound(s) and Activities........................................................................................................... 85 Reishia clavigera (Küster, 1860) (=Thais clavigera).................................................................................. 85 Biology������������������������������������������������������������������������������������������������������������������������������������������ 85 Compound(s) and Activities........................................................................................................... 85 Phycothais reticulata (Quoy and Gaimard, 1833)....................................................................................... 85 Biology������������������������������������������������������������������������������������������������������������������������������������������ 86 Compound(s) and Activities........................................................................................................... 86 Drupella fragum (Blainville, 1832)............................................................................................................. 86 Biology������������������������������������������������������������������������������������������������������������������������������������������ 86 Compound(s) and Activities........................................................................................................... 86

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Drupella margariticola (Broderip, 1833) (=Drupa margariticola)............................................................ 86 Biology������������������������������������������������������������������������������������������������������������������������������������������ 86 Compound(s) and Activities........................................................................................................... 86 Dicathais orbita (Gmelin, 1791)................................................................................................................. 87 Biology������������������������������������������������������������������������������������������������������������������������������������������ 87 Compound(s) and Activities........................................................................................................... 87 Chicoreus ramosus (Linnaeus, 1758).......................................................................................................... 88 Biology������������������������������������������������������������������������������������������������������������������������������������������ 88 Compound(s) and Activities........................................................................................................... 88 Chicoreus virgineus (Röding, 1798) (=Murex virgineus)............................................................................ 89 Biology������������������������������������������������������������������������������������������������������������������������������������������ 89 Compound(s) and Activities........................................................................................................... 89 Chicoreus sp................................................................................................................................................ 89 Compound(s) and Activities........................................................................................................... 89 Tenguella marginalba (Blainville, 1832)..................................................................................................... 89 Biology������������������������������������������������������������������������������������������������������������������������������������������ 89 Compound(s) and Activities........................................................................................................... 90 Concholepas concholepas (Bruguière, 1789) ............................................................................................. 90 Biology������������������������������������������������������������������������������������������������������������������������������������������ 90 Compound(s) and Activities........................................................................................................... 90 Pleuroploca trapezium (Linnaeus, 1758).................................................................................................... 90 Biology������������������������������������������������������������������������������������������������������������������������������������������ 90 Compound(s) and Activities........................................................................................................... 90 Marmorofusus nicobaricus (Röding, 1798) (=Fusinus nicobaricus).......................................................... 91 Biology������������������������������������������������������������������������������������������������������������������������������������������ 91 Compound(s) and Activities........................................................................................................... 91 Oxymeris maculata (Linnaeus, 1758) (=Terebra muculata)....................................................................... 92 Biology������������������������������������������������������������������������������������������������������������������������������������������ 92 Compound(s) and Activities........................................................................................................... 92 Terebra argus (Hinds, 1844)........................................................................................................................ 92 Biology������������������������������������������������������������������������������������������������������������������������������������������ 92 Compound(s) and Activities........................................................................................................... 92 Terebra consobrina (Deshayes, 1857)......................................................................................................... 92 Compound(s) and Activities........................................................................................................... 92 Melo melo (Lightfoot, 1786) (=Cymbium melo)���������������������������������������������������������������������������������������� 93 Biology������������������������������������������������������������������������������������������������������������������������������������������ 93 Compound(s) and Activities........................................................................................................... 93 Cymbiola vespertilo (Linnaeus, 1758)........................................................................................................ 93 Biology������������������������������������������������������������������������������������������������������������������������������������������ 93 Compound(s) and Activities........................................................................................................... 93 Kelletia kelletii (Forbes, 1850) (=Fusus kelletii)......................................................................................... 93 Biology������������������������������������������������������������������������������������������������������������������������������������������ 94 Compound(s) and Activities........................................................................................................... 94 Buccinum undatum (Linnaeus, 1758).......................................................................................................... 94 Biology������������������������������������������������������������������������������������������������������������������������������������������ 94 Compound(s) and Activities........................................................................................................... 95 Buccinum sp................................................................................................................................................. 95 Biology������������������������������������������������������������������������������������������������������������������������������������������ 95 Harpa major (Röding, 1798) (=Harpa conoidalis)..................................................................................... 95 Biology������������������������������������������������������������������������������������������������������������������������������������������ 95 Compound(s) and Activities........................................................................................................... 95 Babylonia japonica (Reeve, 1842).............................................................................................................. 96 Compound(s) and Activities........................................................................................................... 96 Babylonia spirata (Linnaeus, 1758)............................................................................................................ 96 Biology������������������������������������������������������������������������������������������������������������������������������������������ 96 Compound(s) and Activities........................................................................................................... 96

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Babylonia zeylanica (Bruguière, 1789)....................................................................................................... 97 Biology������������������������������������������������������������������������������������������������������������������������������������������ 97 Compound(s) and Activities........................................................................................................... 97 Conus betulinus (Linnaeus, 1758)............................................................................................................... 97 Biology������������������������������������������������������������������������������������������������������������������������������������������ 98 Compound(s) and Activities........................................................................................................... 98 Conus bullatus (Linnaeus, 1758)................................................................................................................. 98 Compound(s) and Activities........................................................................................................... 98 Conus catus (Hwass in Bruguière, 1792).................................................................................................... 98 Compound(s) and Activities........................................................................................................... 99 Conus consors (Sowerby I, 1833)............................................................................................................... 99 Compound(s) and Activities........................................................................................................... 99 Conus geographus (Linnaeus, 1758)........................................................................................................... 99 Compound(s) and Activities........................................................................................................... 99 Conus gloriamaris (Chemnitz, 1777).......................................................................................................... 99 Compound(s) and Activities........................................................................................................... 99 Conus inscriptus (Reeve, 1843)................................................................................................................... 99 Compound(s) and Activities......................................................................................................... 100 Conus kinoshitai (Kuroda, 1956).............................................................................................................. 100 Compound(s) and Activities......................................................................................................... 100 Conus magus (Linnaeus, 1758)................................................................................................................. 100 Compound(s) and Activities......................................................................................................... 100 Conus marmoreus (Linnaeus, 1758)..........................................................................................................101 Biology���������������������������������������������������������������������������������������������������������������������������������������� 101 Compound(s) and Activities..........................................................................................................101 Conus miles (Linnaeus, 1758)....................................................................................................................101 Biology���������������������������������������������������������������������������������������������������������������������������������������� 101 Compound(s) and Activities..........................................................................................................101 Conus planorbis (Born, 1778)....................................................................................................................101 Compound(s) and Activities..........................................................................................................101 Conus purpurascens (Sowerby I, 1833).....................................................................................................101 Compound(s) and Activities......................................................................................................... 102 Conus radiatus (Gmelin, 1791)................................................................................................................. 102 Compound(s) and Activities......................................................................................................... 102 Conus stercusmuscarum (Linnaeus, 1758)................................................................................................ 102 Biology���������������������������������������������������������������������������������������������������������������������������������������� 102 Compound(s) and Activities......................................................................................................... 102 Conus striatus (Linnaeus, 1758)................................................................................................................ 102 Compound(s) and Activities......................................................................................................... 103 Conus ventricosus (Gmelin, 1791)............................................................................................................ 103 Compound(s) and Activities......................................................................................................... 103 Conus victoriae (Reeve, 1843).................................................................................................................. 103 Compound(s) and Activities......................................................................................................... 103 Euchelus asper (Gmelin, 1791)................................................................................................................. 104 Biology���������������������������������������������������������������������������������������������������������������������������������������� 104 Compound(s) and Activities......................................................................................................... 104 Nerita albicilla (Linnaeus, 1758).............................................................................................................. 104 Biology���������������������������������������������������������������������������������������������������������������������������������������� 104 Compound(s) and Activities......................................................................................................... 104 Tectus niloticus (Linnaeus, 1767).............................................................................................................. 104 Biology���������������������������������������������������������������������������������������������������������������������������������������� 105 Compound(s) and Activities......................................................................................................... 105 Tectus tentorium (Gmelin, 1791) (=Trochus tentorium)............................................................................ 105 Biology���������������������������������������������������������������������������������������������������������������������������������������� 105 Compound(s) and Activities......................................................................................................... 105

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Tegula gallina (Forbes, 1850).................................................................................................................... 105 Biology���������������������������������������������������������������������������������������������������������������������������������������� 106 Compound(s) and Activities......................................................................................................... 106 Trochus radiatus (Gmelin, 1791)............................................................................................................... 106 Biology���������������������������������������������������������������������������������������������������������������������������������������� 106 Compound(s) and Activities......................................................................................................... 106 Lunella coronata (Gmelin, 1791) (=Turbo coronatus).............................................................................. 106 Biology���������������������������������������������������������������������������������������������������������������������������������������� 107 Compound(s) and Activities......................................................................................................... 107 Turbo bruneus (Röding, 1791).................................................................................................................. 107 Biology���������������������������������������������������������������������������������������������������������������������������������������� 107 Compound(s) and Activities......................................................................................................... 107 Turbo marmoratus (Linnaeus, 1758)......................................................................................................... 108 Biology���������������������������������������������������������������������������������������������������������������������������������������� 109 Compound(s) and Activities......................................................................................................... 109 Turbo setosus (Gmelin, 1791)................................................................................................................... 109 Biology���������������������������������������������������������������������������������������������������������������������������������������� 109 Compound(s) and Activities......................................................................................................... 109 Turbo stenogyrus (Fischer, 1873).............................................................................................................. 109 Biology���������������������������������������������������������������������������������������������������������������������������������������� 110 Compound(s) and Activities..........................................................................................................110 Thuridilla hopei (Verany, 1853).................................................................................................................111 Biology���������������������������������������������������������������������������������������������������������������������������������������� 111 Compound(s) and Activities..........................................................................................................111 Thuridilla splendens (Baba, 1949).............................................................................................................112 Biology���������������������������������������������������������������������������������������������������������������������������������������� 112 Compound(s) and Activities..........................................................................................................112 Elysia grandifolia (Kelaart, 1858)..............................................................................................................112 Biology���������������������������������������������������������������������������������������������������������������������������������������� 112 Compound(s) and Activities..........................................................................................................112 Elysia nisbeti (Thompson, 1977)................................................................................................................113 Biology���������������������������������������������������������������������������������������������������������������������������������������� 113 Compound(s) and Activities..........................................................................................................113 Elysia ornata (Swainson, 1840).................................................................................................................113 Biology���������������������������������������������������������������������������������������������������������������������������������������� 113 Compound(s) and Activities..........................................................................................................113 Elysia patina (Ev. Marcus, 1980)...............................................................................................................114 Biology���������������������������������������������������������������������������������������������������������������������������������������� 114 Compound(s) and Activities..........................................................................................................114 Elysia rufescens (Pease, 1871)...................................................................................................................114 Biology���������������������������������������������������������������������������������������������������������������������������������������� 115 Compound(s) and Activities..........................................................................................................115 Elysia subornata (Verrill, 1901).................................................................................................................116 Biology���������������������������������������������������������������������������������������������������������������������������������������� 117 Compound(s) and Activities..........................................................................................................117 Plakobranchus ocellatus (van Hasselt, 1824)............................................................................................117 Biology���������������������������������������������������������������������������������������������������������������������������������������� 117 Compound(s) and Activities..........................................................................................................117 Cyerce nigricans (Pease, 1866)..................................................................................................................118 Biology���������������������������������������������������������������������������������������������������������������������������������������� 118 Compound(s) and Activities..........................................................................................................118 Onchidium sp. (1).......................................................................................................................................118 Biology���������������������������������������������������������������������������������������������������������������������������������������� 118 Compound(s) and Activities..........................................................................................................119 Onchidium sp. (2).......................................................................................................................................119 Compound(s) and Activities..........................................................................................................119

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Onchidium sp. (3).......................................................................................................................................119 Compound(s) and Activities..........................................................................................................119 Onchidium sp. (4).......................................................................................................................................119 Compound(s) and Activities..........................................................................................................119 Pleurobranchus albiguttatus (Bergh, 1905)...............................................................................................119 Biology���������������������������������������������������������������������������������������������������������������������������������������� 120 Compound(s) and Activities......................................................................................................... 120 Pleurobranchus forskalii (Ruppell and Leuckart, 1828)........................................................................... 120 Biology���������������������������������������������������������������������������������������������������������������������������������������� 120 Compound(s) and Activities......................................................................................................... 120 Pleurobranchus membranaceus (Montagu, 1815)����������������������������������������������������������������������������������� 121 Biology���������������������������������������������������������������������������������������������������������������������������������������� 121 Compound(s) and Activities......................................................................................................... 121 Tylodina perversa (Gmelin, 1791)............................................................................................................. 122 Biology���������������������������������������������������������������������������������������������������������������������������������������� 122 Compound(s) and Activities......................................................................................................... 122 Bursatella leachii (de Blainville, 1817)..................................................................................................... 122 Biology���������������������������������������������������������������������������������������������������������������������������������������� 122 Compound(s) and Activities......................................................................................................... 123 Aplysia argus (Ruppell and Leuckart, 1830) (=Aplysia angasi)............................................................... 123 Biology���������������������������������������������������������������������������������������������������������������������������������������� 123 Compound(s) and Activities......................................................................................................... 123 Aplysia dactylomela (Rang, 1828)............................................................................................................ 124 Biology���������������������������������������������������������������������������������������������������������������������������������������� 124 Compound(s) and Activities......................................................................................................... 124 Aplysia depilans (Gmelin, 1791)............................................................................................................... 126 Biology���������������������������������������������������������������������������������������������������������������������������������������� 126 Compound(s) and Activities......................................................................................................... 127 Aplysia fasciata (Poiret, 1789).................................................................................................................. 127 Biology���������������������������������������������������������������������������������������������������������������������������������������� 127 Compound(s) and Activities......................................................................................................... 127 Aplysia kurodai (Baba, 1937).................................................................................................................... 128 Biology���������������������������������������������������������������������������������������������������������������������������������������� 128 Compound(s) and Activities......................................................................................................... 128 Aplysia oculifera (Adams and Reeve, 1850)............................................................................................. 130 Biology���������������������������������������������������������������������������������������������������������������������������������������� 130 Compound(s) and Activities......................................................................................................... 130 Aplysia punctata (Cuvier, 1803)��������������������������������������������������������������������������������������������������������������� 131 Biology���������������������������������������������������������������������������������������������������������������������������������������� 131 Compound(s) and Activities..........................................................................................................131 Dolabella auricularia (Lightfoot, 1786)................................................................................................... 132 Biology���������������������������������������������������������������������������������������������������������������������������������������� 132 Compound(s) and Activities......................................................................................................... 132 Dolabrifera dolabrifera (Rang, 1828)....................................................................................................... 135 Biology���������������������������������������������������������������������������������������������������������������������������������������� 135 Compound(s) and Activities......................................................................................................... 136 Stylocheilus longicauda (Quoy and Gaimard, 1824) (=Stylocheilus citrina)............................................ 136 Biology���������������������������������������������������������������������������������������������������������������������������������������� 136 Compound(s) and Activities......................................................................................................... 136 Stylocheilus sp........................................................................................................................................... 137 Compound(s) and Activities......................................................................................................... 137 Tambja ceutae (Garcia-Gomez and Ortea, 1988)...................................................................................... 137 Biology���������������������������������������������������������������������������������������������������������������������������������������� 137 Compound(s) and Activities......................................................................................................... 137 Tambja eliora (Marcus and Marcus, 1967)............................................................................................... 138 Biology���������������������������������������������������������������������������������������������������������������������������������������� 138 Compound(s) and Activities......................................................................................................... 138

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Tyrannodoris tigris (Farmer, 1978) (=Roboastra tigris)........................................................................... 138 Biology���������������������������������������������������������������������������������������������������������������������������������������� 139 Compound(s) and Activities......................................................................................................... 139 Tritoniopsis elegans (Audouin, 1826) (=Tritoniopsilla alba)................................................................... 139 Biology���������������������������������������������������������������������������������������������������������������������������������������� 139 Compound(s) and Activities......................................................................................................... 139 Tochuina tetraquetra (Pallas, 1788).......................................................................................................... 139 Biology���������������������������������������������������������������������������������������������������������������������������������������� 140 Compound(s) and Activities......................................................................................................... 140 Marionia limceana (Silva, de Meirelles, and Matthews-Cascon, 2013)................................................... 140 Biology���������������������������������������������������������������������������������������������������������������������������������������� 140 Compound(s) and Activities......................................................................................................... 140 Phidiana militaris (Alder and Hancock, 1864)..........................................................................................141 Biology���������������������������������������������������������������������������������������������������������������������������������������� 141 Compound(s) and Activities..........................................................................................................141 Peltodoris atromaculata (Bergh, 1880) (=Discodoris atromaculata)........................................................141 Biology���������������������������������������������������������������������������������������������������������������������������������������� 141 Compound(s) and Activities..........................................................................................................141 Peltodoris nobilis (MacFarland, 1905) (=Anisodoris nobilis; Montereina nobilis).................................. 142 Biology���������������������������������������������������������������������������������������������������������������������������������������� 142 Compound(s) and Activities......................................................................................................... 142 Doris fontainii (d’Orbigny, 1837) (=Anisodoris fontaini)......................................................................... 142 Biology���������������������������������������������������������������������������������������������������������������������������������������� 142 Compound(s) and Activities..........................................................................................................143 Doris kerguelenensis (Bergh, 1884) (=Austrodoris kerguelenensis)..........................................................143 Biology���������������������������������������������������������������������������������������������������������������������������������������� 143 Compound(s) and Activities..........................................................................................................143 Archidoris montereyensis (Cooper, 1862)................................................................................................. 144 Biology���������������������������������������������������������������������������������������������������������������������������������������� 144 Compound(s) and Activities......................................................................................................... 144 Jorunna funebris (Kelaart, 1858).............................................................................................................. 145 Biology���������������������������������������������������������������������������������������������������������������������������������������� 145 Compound(s) and Activities......................................................................................................... 145 Glossodoris rufomarginata (Bergh, 1890)(=Chromodoris youngbleuthi)................................................ 145 Biology���������������������������������������������������������������������������������������������������������������������������������������� 146 Compound(s) and Activities......................................................................................................... 146 Goniobranchus cavae (Eliot, 1904) (=Chromodoris cavae)......................................................................147 Biology���������������������������������������������������������������������������������������������������������������������������������������� 147 Compound(s) and Activities..........................................................................................................147 Goniobranchus obsoletus (Rüppell and Leuckart, 1830) (=Chromodoris obsoleta).................................147 Biology���������������������������������������������������������������������������������������������������������������������������������������� 147 Compound(s) and Activities..........................................................................................................147 Goniobranchus splendidus (Angas, 1864)����������������������������������������������������������������������������������������������� 148 Biology���������������������������������������������������������������������������������������������������������������������������������������� 148 Compound(s) and Activities......................................................................................................... 148 Chromodoris annae (Bergh, 1877)............................................................................................................ 149 Biology���������������������������������������������������������������������������������������������������������������������������������������� 149 Compound(s) and Activities......................................................................................................... 149 Chromodoris aspersa (Gould, 1852) (=Chromodoris inornata)............................................................... 150 Biology���������������������������������������������������������������������������������������������������������������������������������������� 150 Compound(s) and Activities......................................................................................................... 150 Chromodoris lochi (Rudman, 1982).......................................................................................................... 150 Biology���������������������������������������������������������������������������������������������������������������������������������������� 151 Compound(s) and Activities......................................................................................................... 151 Chromodoris quadricolor (Ruppell and Leuckart, 1828) (=Glossodoris quadricolor)............................ 151 Biology���������������������������������������������������������������������������������������������������������������������������������������� 151 Compound(s) and Activities......................................................................................................... 151

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Hypselodoris infucata (Rüppell and Leuckart, 1831)............................................................................... 152 Biology���������������������������������������������������������������������������������������������������������������������������������������� 152 Compound(s) and Activities......................................................................................................... 152 Halgerda stricklandi (Fahey and Gosliner, 1999)..................................................................................... 152 Biology���������������������������������������������������������������������������������������������������������������������������������������� 152 Compound(s) and Activities......................................................................................................... 152 Diaulula sandiegensis (Cooper, 1863)...................................................................................................... 152 Biology���������������������������������������������������������������������������������������������������������������������������������������� 153 Compound(s) and Activities......................................................................................................... 153 Dendrodoris fumata (Ruppell and Leuckart, 1831).................................................................................. 153 Biology���������������������������������������������������������������������������������������������������������������������������������������� 153 Compound(s) and Activities......................................................................................................... 153 Dendrodoris limbata (Cuvier, 1804)......................................................................................................... 153 Biology���������������������������������������������������������������������������������������������������������������������������������������� 154 Compound(s) and Activities......................................................................................................... 154 Armina babai (Tchang, 1934)................................................................................................................... 154 Biology���������������������������������������������������������������������������������������������������������������������������������������� 154 Compound(s) and Activities......................................................................................................... 154 Actinocyclus papillatus (Bergh, 1878)...................................................................................................... 155 Biology���������������������������������������������������������������������������������������������������������������������������������������� 155 Compound(s) and Activities......................................................................................................... 155 Acanthodoris nanaimoensis (O’Donoghue, 1921).................................................................................... 155 Biology���������������������������������������������������������������������������������������������������������������������������������������� 155 Compound(s) and Activities......................................................................................................... 155 Adalaria loveni (Alder and Hancock, 1862)............................................................................................. 155 Biology���������������������������������������������������������������������������������������������������������������������������������������� 155 Compound(s) and Activities......................................................................................................... 156 Aldisa andersoni (Gosliner and Behrens, 2004)........................................................................................ 156 Biology���������������������������������������������������������������������������������������������������������������������������������������� 156 Compound(s) and Activities......................................................................................................... 156 Hexobranchus sanguineus (Ruppell and Leuckart, 1828)......................................................................... 156 Biology���������������������������������������������������������������������������������������������������������������������������������������� 156 Compound(s) and Activities......................................................................................................... 157 Leminda millecra (Griffiths, 1985)............................................................................................................ 158 Biology���������������������������������������������������������������������������������������������������������������������������������������� 158 Compound(s) and Activities......................................................................................................... 158 Notodoris gardineri (Eliot, 1906).............................................................................................................. 158 Biology���������������������������������������������������������������������������������������������������������������������������������������� 158 Compound(s) and Activities......................................................................................................... 158 Phyllodesmium briareum (Bergh, 1896)................................................................................................... 159 Biology���������������������������������������������������������������������������������������������������������������������������������������� 159 Compound(s) and Activities......................................................................................................... 159 Phyllodesmium magnum (Rudman, 1991)................................................................................................ 159 Biology���������������������������������������������������������������������������������������������������������������������������������������� 160 Compound(s) and Activities......................................................................................................... 160 Phyllidia coelestis (Bergh, 1905).............................................................................................................. 160 Biology���������������������������������������������������������������������������������������������������������������������������������������� 160 Compound(s) and Activities......................................................................................................... 160 Phyllidia ocellata (Cuvier, 1804).............................................................................................................. 160 Biology���������������������������������������������������������������������������������������������������������������������������������������� 161 Compound(s) and Activities..........................................................................................................161 Phyllidiella pustulosa (Cuvier, 1804).........................................................................................................161 Biology���������������������������������������������������������������������������������������������������������������������������������������� 161 Compound(s) and Activities..........................................................................................................161 Reticulidia fungia (Brunckhorst and Gosliner in Brunckhorst, 1993)...................................................... 162 Biology���������������������������������������������������������������������������������������������������������������������������������������� 162 Compound(s) and Activities......................................................................................................... 162

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2.3 Class: Cephalopoda................................................................................................................................... 162 Sepioteuthis lessoniana (Férussac, 1831).................................................................................................. 162 Biology���������������������������������������������������������������������������������������������������������������������������������������� 162 Compound(s) and Activities......................................................................................................... 163 Doryteuthis (Amerigo) pealeii (Lesueur, 1821) (=Loligo pealii).............................................................. 163 Biology���������������������������������������������������������������������������������������������������������������������������������������� 163 Compound(s) and Activities......................................................................................................... 163 Uroteuthis duvaucelii (d’Orbigny [in Férussac & d’Orbigny], 1835) (=Loligo duvauceli)...................... 164 Biology���������������������������������������������������������������������������������������������������������������������������������������� 164 Compound(s) and Activities......................................................................................................... 164 Loligo vulgaris (Lamarck, 1798)............................................................................................................... 164 Biology���������������������������������������������������������������������������������������������������������������������������������������� 165 Compound(s) and Activities......................................................................................................... 165 Loligo sp.................................................................................................................................................... 165 Dosidicus gigas (Orbigny, 1835)............................................................................................................... 165 Biology���������������������������������������������������������������������������������������������������������������������������������������� 165 Compound(s) and Activities......................................................................................................... 165 Ommastrephes bartramii (Lesueur, 1821)................................................................................................. 166 Biology���������������������������������������������������������������������������������������������������������������������������������������� 166 Compound(s) and Activities......................................................................................................... 166 Sepia aculeata (Van Hasselt, 1835)........................................................................................................... 166 Biology���������������������������������������������������������������������������������������������������������������������������������������� 166 Compound(s) and Activities......................................................................................................... 167 Sepia brevimana (Steenstrup, 1875).......................................................................................................... 167 Biology���������������������������������������������������������������������������������������������������������������������������������������� 167 Compound(s) and Activities......................................................................................................... 167 Sepia esculenta (Hoyle, 1885)................................................................................................................... 167 Biology���������������������������������������������������������������������������������������������������������������������������������������� 168 Compound(s) and Activities......................................................................................................... 168 Sepia kobiensis (Hoyle, 1885)................................................................................................................... 168 Biology���������������������������������������������������������������������������������������������������������������������������������������� 168 Compound(s) and Activities......................................................................................................... 168 Sepia officinalis (Linnaeus, 1758)............................................................................................................. 169 Biology���������������������������������������������������������������������������������������������������������������������������������������� 169 Compound(s) and Activities......................................................................................................... 169 Sepia pharaonis (Ehrenberg, 1831)............................................................................................................170 Biology���������������������������������������������������������������������������������������������������������������������������������������� 170 Compound(s) and Activities..........................................................................................................170 Sepiella inermis (Van Hasselt, 1835)..........................................................................................................170 Biology���������������������������������������������������������������������������������������������������������������������������������������� 171 Compound(s) and Activities..........................................................................................................171 Octopus cyaneus (Gray, 1849)...................................................................................................................171 Biology���������������������������������������������������������������������������������������������������������������������������������������� 171 Compound(s) and Activities......................................................................................................... 172 Octopus vulgaris (Cuvier, 1797)............................................................................................................... 172 Biology���������������������������������������������������������������������������������������������������������������������������������������� 172 Compound(s) and Activities......................................................................................................... 172 Amphioctopus aegina (Gray, 1849) (=Octopus aegina)��������������������������������������������������������������������������� 173 Biology���������������������������������������������������������������������������������������������������������������������������������������� 173 Compound(s) and Activities..........................................................................................................173 Paroctopus limaculatus (Authority, not known).........................................................................................173 Biology���������������������������������������������������������������������������������������������������������������������������������������� 173 Compound(s) and Activities..........................................................................................................173 References..................................................................................................................................................................................175 Index.......................................................................................................................................................................................... 189

Preface Marine life has great potential for the development of new drugs. Bioactive substances isolated from marine invertebrates such as poriferans, coelenterates, mollusks, echinoderms, bryozoans, and tunicates have been reported to possess antiviral, antimicrobial, antiprotozoal, antifungal, antihelmintic, and anticancer activities. Marine natural products have attracted the attention of biologists and chemists all over the world for the last five decades. The number of natural products isolated from marine organisms increases rapidly and now exceeds 18,000. Among marine invertebrates, marine mollusks assume greater significance owing to their commercial applications, viz. as a source of food and ornaments and for the production of lime. A few species of mollusks have also been reported to act as scavengers, cleaning the environment and serving as pollution indicators. Of late, many molluskan species have been identified as a potential source of secondary metabolites, having a wide range of pharmaceutical applications. Compounds such as alkaloids, carotenoids, and conotoxins derived from marine mollusks have been tested successfully for their strong bioactive characteristics. Dolatriol, isolated from the marine mollusk Dollabella auricularia , has pronounced antileukemic activity. Aplysistatin is a well-known antileukemic metabolite from the sea hare Aplysia angasi . The metabolites of Aplysia dactylomela  have been reported to possess cytotoxic and antitumor activity in vivo. The bioactive compound Zinconitide, isolated from the marine snail Conus magnus , is licensed by Elan Pharmaceuticals under the name Prialt®  and is used for intratracheal treatment for chronic pain. Dollastatins isolated from the sea hare Dolabella auricularia  have antitumor properties. An HIV-inhibiting compound has been isolated from the green mussel Perna viridis  . Kelletinin I and II isolated from Kelletia kelletii  inhibited the growth of Bacillus subtilis  and

L1 leukemia cells as antibacterial and anticancer agents. Surugatoxin and neosurugatoxin isolated from Japanese ivory shell Babylonia japonica  exhibited antinicotinic activity. A potential polysaccharide with potent antibacterial and antifungal activity was extracted from the cuttlebone of Sepia aculeata  and Sepia brevimana . Though a few books are presently available on marine natural products, a comprehensive book on the “ Biology and Ecology of Pharmaceutical Marine Mollusks”  has not so far been published. This publication, the first of its kind contributed by scientists of both the marine biology and pharmacy disciplines, is intended to meet this long-felt need. The taxonomy, common name, global distribution, habitat, diagnostic features, and pharmaceutical compounds (along with their activities) of 275 species of marine mollusks are given, along with suitable illustrations. It is hoped that the present publication, when brought out, will be of great use: as a standard reference for researchers, teachers, and students of various disciplines such as fisheries science, marine biology, marine ecology, biochemistry, biotechnology, and pharmacy; in libraries of colleges, universities, and institutions; and as a valuable guide for pharmaceutical companies involved in the development of new drugs from marine mollusks. We are highly indebted to Dr. K. Venkataramanujam, former dean of the Fisheries College and Research Institute, Tamilnadu Veterinary and Animal Sciences University, Thoothukudi, India, for his valued comments and suggestions on the manuscript. We sincerely thank all our international friends who were kind enough to collect and send certain species of marine mollusks for the present purpose. The services, viz. photography and secretarial assistance, rendered by Mrs. Albin Panimalar Ramesh, are also gratefully acknowledged.

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Authors Dr. Ramasamy Santhanam  is a former dean of the Fisheries College and Research Institute, Tamilnadu Veterinary and Animal Sciences University, Thoothukudi, India. His fields of specialization are the fisheries environment and marine biology. He presently serves as a fisheries expert for various government and nongovernment organizations in India. Dr. Santhanam has published 23 books on various aspects of fisheries science, as well as 70 research papers. He was a member of the American Fisheries Society, United States; World Aquaculture Society, United States; Global Fisheries Ecosystem Management Network (GFEMN), United States; and IUCN’  s Commission on Ecosystem Management, Switzerland. Dr. Manavalan Gobinath  , principal at the Ratnam Institute of Pharmacy, Nellore, AP, India, obtained his Ph.D. from the department of Pharmaceutical Engineering and Technology, Bharathidasan University, Trichy, India, in 2014. His field of specialization is the phytochemical and pharmacological evaluation of medicinal plants. Dr. Gobinath has 22  years of teaching/research experience and has published

25 research papers in peer-reviewed journals. Presently, he serves as a member of the International Congress in Chemistry and Pharmacy and the Indian Pharmaceutical Association. Dr. Santhanam Ramesh , professor at the Department of Pharmaceutics, Ratnam Institute of Pharmacy, Nellore, AP, India, obtained his Ph.D. from Jawaharlal Nehru Technological University, Hyderabad, India, in 2011. His fields of specialization are biopharmaceutical products, pharmaceutical nanotechnology, and novel drug delivery systems. Dr. Ramesh has 13   years of teaching/overseas experience. He has authored five books, Marine Pharmaceutical Compounds , Freshwater Phytopharmaceutical Compounds , Biology and Ecology of Pharmaceutical  Marine Plants , Biology and Ecology of Pharmaceutical Marine Sponges, and A Text Book of Novel Drug Delivery Systems , and he has had ten research papers published in nationally and internationally reputed journals. He presently serves as an associate member of the Academy Pharmacy Group, Royal Pharmaceutical Society, Great Britain, and as a Fellow of the Institution of Chemists, India.

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1

Introduction

The enormous ecological resources of the seas and oceans have been exploited since ancient times, and natural medicinal products have been used for millennia for the treatment of multiple ailments. Although many have been superseded by conventional pharmaceutical approaches, there is currently a resurgence in interest in the use of natural products by the general public, which forms the basis of a worldwide, multi-million-dollar major commercial industry. In addition, the pharmaceutical industry continues to examine the potential of natural products as sources of novel medicinal compounds. Diversity of marine pharmaceutical fauna and flora: Marine invertebrates such as sponges, bryozoans, corals, mollusks, and ascidians constitute 62% of pharmaceutical marine life, and the remaining 38% is made up of microorganisms such as actinomycetes, fungi, dinoflagellates, and cyanobacteria​. Marine natural products: Marine organisms are reservoirs of structurally diverse bioactive materials with numerous biological effects on the human body. These bioactive materials include polysaccharides (agar, alginates, carrageenan, fucoidan, ulvan, laminarin, porphyran, and fulcellaran); pigments (chlorophyll, carotenoids, and phycobillins); protein and peptides; polyunsaturated fatty acids (PUFA); polyphenols; and other bioactive compounds (Pangestuti and Kim, 2017). Therapeutic properties: Marine-derived natural products have an extensive array of therapeutic properties, including antimicrobial (antibacterial and antifungal), antiinflammatory, antioxidant, antiviral, anticancer, antitumor, antileukemia, antiparasitic, antimalarial, neuroprotective, analgesic, anticoagulant, wound-healing and immune-modulating, antihypertensive, and other medicinal properties. A number of marine natural products have provided important leads for drug development, and many are now used in the formulation of novel drugs (Ahmad et al., 2018) Present status of marine pharmacology: So far, more than 30,000 compounds with unique structures and diverse pharmacological activities have been isolated from the marine plants and invertebrates. Since 1967, more than 18,000 new metabolites have been isolated and more than 400 patents have been obtained (Anon., http:​ //www​ .marb​ ef.or​g/pro​jects​/rose​meb/p​resen​tatio​ns/Fo​ntana​.pdf)​. Some of these compounds that have been extracted and studied show effects against deadly diseases, including HIV and cancer. However, only a few marine-based drugs are currently on the market, including: Prialt®, a potent analgesic; Yondelis, Cytosar-U, Adcetris, and Halaven, antitumor agents; Vira-A and Carragelose, antiviral agents; and Lovaza, a treatment for hypertriglyceridemia. Other potential candidates include Scytonemin, a pigment isolated from cyanobacteria, which

inhibits cell cycle-regulatory kinases, with the potential to cure hyperproliferative disorders with no chemical toxicity. Marine Natural Products in Pharmaceutical Pipeline (as of 2011) FDA-approved drugs

7

Clinical trials Preclinical research

11 1458

Published marine natural products

8940

Source: Kingston (2013).

PHARMACEUTICAL MARINE MOLLUSKS The phylum Mollusca is of particular interest as a source of new potential drug leads. These mollusks encompass 7% of living animals on the planet, making them the second largest animal phylum (Ahmad et al., 2018; Ramesh et al., 2012). Marine mollusks can be found from tropical seas and temperate waters to Artic–Antarctic regions, showing different morphologies and occupying a wide range of ecological niches. They feed on a wide variety of benthic invertebrates and plants, often accumulating dietary metabolites from their prey to be reused against their own potential predators. Diversity of marine mollusks: The phylum Mollusca has seven classes: Class Bivalvia—clams, oysters, scallops, mussels Class Gastropoda—snails, slugs, limpets, cowries Class Cephalopoda—octopuses, squid, nautiloids Class Scaphopoda—mollusks with tusk shells Class Polyplacophora—chitons Class Aplacophora—mollusks that lack shells and are wormlike in shape Class Monoplacophora—mollusks with a limpetlike appearance (living fossils) It is interesting to note that most of the chemical studies on marine natural products have been focused on gastropods, (which are traditionally divided in three major groups: the subclasses Prosobranchia, Pulmonata, and Opisthobranchia) and more recently on bivalves. Molluskan-derived natural products: Mollusks have been a significant focus in the search for biologically active secondary metabolites, with >1,145 natural products isolated from just over 270 species of mollusks (~0.3% of 52,525 described species) in the last three decades (Benkendorff, 2010; Dang et al., 2015). Two molluskan-derived natural products have been clinically tested and approved by 1

2

Biology and Ecology of Pharmaceutical Marine Mollusks

the U.S. Food and Drug Administration (FDA). They are Ziconotide (a synthetic version of the peptide ω-conotoxin MVIIA, commercialized under the name of Prialt®), derived from Conus magus to treat chronic pain by blocking N-type voltage gated calcium channels (Duggan and Tuck, 2015); and Brentuximab vedotin, developed for treating lymphoma and Hodgkin’s disease (Mayer et al., 2010). There are at least 18 other compounds originally found in mollusks and associated cyanobacteria that are currently in clinical trials. However, ~52% of the molluskan natural products that have been isolated to date have never been tested for any biological activity (Benkendorff, 2014). Furthermore, 25°C). The condition factor index remained high (>28.0) from April to June (Yurimoto et al., 2008). Compound(s) and Activities Antitumoral and anti-inflammatory activities: P2, a polypeptide fraction, isolated from this species inhibited the proliferation of seven tumor cell lines, especially in HeLa and HT-29 cell lines. The IC50 values were 11.43 μg/ml for HeLa and 13.00 μg/ml for HT-29 treated by P2 for 48 h. The results demonstrated that P2 might be a potential antitumor agent with high efficiency in dose-dependent and time-dependent manners and low toxicity (Hu et al., 2012). Ahmad et al. (2018) reported that the polypeptide fraction (P2) of this species inhibited the production of NO in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage; inhibited the secretion of IL-6 and TNFα in human cervical cancer HeLa cells; downregulated the IL-8; and inhibited the COX-2 and iNOS-related pathways. Antitumoral and antioxidant activities: A new antitumor and antioxidant peptide (H3) has been isolated from this species (Chen et al., 2013). Hypoglycemia and hypolid effects: The hydrolysate isolated from this species has shown hypoglycemia and hypolid effects (Changgui, 1996).

Biology and Ecology of Pharmaceutical Marine Mollusks

Ecology: This benthic species inhabits sand and muddy bottoms at intertidal and sublittoral depths to 25 m. Description: Shell of this species is inequivalve, solid, inequilateral, obliquely ovate, and elongate in outline, with an extended posteroventral part. Umbones are much inflated and are situated rather forwards. About 40 radial ribs are seen at each valve; ribs usually have a narrow median groove on top. Periostracum is coarse and velvety, often eroded on umbones. Internal margins have strong crenulations corresponding with the external radial ribs. Outside of shell is grayish white, often stained darker gray on umbonal and posterior areas; periostracum is dark brown; and inner side is white. It has a maximum length of 10.5 cm. This species is cultivated in commercial fisheries. Biology Food and feeding: It feeds on diatoms and green algae. Reproduction: In this species, gametogenic activity and spawning occur continuously throughout the year, with peak spawning from July to September. Fluctuations of the gonad index suggest that the duration of the gametogenic cycle is 1–2 months. Hermaphroditism has also been reported in this species. Compound(s) and Activities Artificial bones: The bioceramic powder prepared from the shell of this species has been reported to contain high-quality hydroxyapatite and has the potential to be developed as an implant or artificial bone that has similar physical and mechanical properties to natural human bones (Gunawarman et al., 2015).

Anadara satowi (Dunker, 1882)

Anadara antiquata (Linnaeus, 1758)

Order: Arcoida Family: Arcidae Common name: Antique ark Distribution: Indo-Pacific: Eastern Africa to Japan, Australia, eastern Polynesia, and Hawaii

Order: Arcoida Family: Arcidae Common name: Ark shell Distribution: Native to the Northwest Pacific: From Hong Kong, China to Hokkaido, Japan Ecology: It inhabits muddy, subtidal environments and it may occasionally attach to rocks and shells using its byssus threads. Description: It has a thick, strongly ribbed shell. The hinge line bears numerous teeth, arranged in a line on both valves.

5

Marine Mollusks

Both valves have prominent beaks which almost come into contact with each other. Shell is heart-shaped in a side view. It is covered with brown periostracum and it may reach a size of 90+ mm. Biology Food and feeding: It is a suspension feeder, utilizing a mixture of benthic microalgae and coastal phytoplankton. Reproduction: Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Immunological activity: The hemoglobins Hb I and Hb II of this species have shown immunological activities (Ohnoki et al., 1973).

Tegillarca granosa (Linnaeus, 1758) (=Arca granosa)

Reproduction: It reproduces from August to February of the following year and reaches maturity at the age of 1–2 yrs. One female can produce 518,400–2,313,200 eggs. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Anticancer activity: The active natural extract haishengsu, which can be isolated from this species, has been found to inhibit the proliferation of human hepatocellular carcinoma BEL-7402 cells in a dose- and time-dependent manner (Chen et al., 2015). Orthopedic applications: The hydroxyapatite compound derived from the shells of this species could have potential orthopedic and biomedical applications (Khiri et al., 2016). Others: Ramasamy and Balasubramanian (2012) reported on the isolated compounds of this species, and their activities are detailed below.

Bioactive Compound

Activity

3-Phe​nyl-2​,3-di​hydro​benzo​[b]-f​ uran-​2-ol—​furan​ compound

Antimicrobial

n-Hexadecenoic acid

Antioxidant, hyporcholesterolemic, and hemolytic Antidiabetic, antiasthma, anticancer, and anti-heart disease Analgesic, anesthetic, antioxidant, antiseptic, antibacterial, antiviral, diuretic, cancer-preventive, and vasodilator

4,7,10,13,16,19-Docosahexaenoic acid Phenol, 2,4-bis (1-phenylethyl)

Order: Arcoida Family: Arcidae Common name: Blood cockle, blood clam, granular ark Distribution: Indo-Pacific: From the eastern coast of South Africa northwards and eastwards to Southeast Asia, Australia, and Polynesia and up to northern Japan Ecology: It lives mainly in intertidal and shallow subtidal waters; burrows down into sand or mud; and lives mainly in protected bays and estuaries, or in mangroves, at a depth range of 0–20 m. Description: Shell of this species is equivalve, thick and solid, ovate, strongly inflated, slightly longer than high, and feebly inequilateral. Umbones are strongly protruding, and cardinal area is rather large. Each valve has 18 radial ribs with wide interstices; ribs are stout and distinctly rugose, bearing regular, often rectangular, nodules. Periostracum is rather thin and smooth. Internal margins have strong crenulations corresponding with the external radial ribs. Outside of shell is white under the yellowish-brown periostracum. Inner side is white, often tinged yellow towards the umbonal cavity. Shell attains a maximum length of 9 cm. Biology Food and feeding: It is a filter feeder. Its important nutrient components are organic detritus (98%), phytoplankton, and unicellular algae.

1,2-Benzenedicaryboxylic acid

Antimicrobial

Source:  Ramasamy and Balasubramanian (2012).

  n-Hexadecenoic acid

acid 4,7,10,13,16,19-Docosahexaenoic

      Phenol, 2,4-bis (1-phenylethyl)  1,2-Benzenedicaryboxylic acid

6

Tegillarca rhombea (Born, 1778) (=Anadara rhombea)

Order: Arcoida Family: Arcidae Common name: Ribbed clam Distribution: Throughout the world’s oceans Ecology: It is an intertidal species that naturally lives in areas with silty bottoms. Biology: A. rhombea differs from A. granosa in having a dirty black shell with, at times, a hairy periostracum, which is quite persistent on the posterior end, and it has narrow umbones. Hinge margin is slightly arched. Radial ribs are not deeply set and devoid of prominent transverse ridges, but are coarse. Ribs on anterior end are considerably smooth. Shell is equivalve with 25 ± 1 ribs. Relatively greater height in relation to length gives the rhomboid ark-shell a gibbose shape, hence the name Anadara rhombea. Shell reaches a maximum size of 62 mm. Biology Food and feeding: As in T. granosa. Reproduction: In this species, the males reach first maturity at 22 mm and females at 24 mm. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antifungal effects: The methanol extracts of the blood of this species showed significant antifungal activity against Candida albicans, Mucor racemosus, and Penicillium expansum (Rajaganapathi et al., 2001).

Cerastoderma edule (Linnaeus, 1758)

Biology and Ecology of Pharmaceutical Marine Mollusks

Distribution: Eastern Atlantic, Mediterranean, and Black Sea: from Portugal to Egypt, north to Norway and Russia then south to Senegal, including Mediterranean and Black Sea Ecology: It occurs in shallow bays, coastal (subtidal zone) waters, and estuarine areas; intertidal muddy sand flats with seagrass meadows, Zostera noltii and Cymodocea nodosa; depth range 0–50 m. Description: Shell of this species is broadly oval with 24 broad ribs and closely spaced concentric ridges; ridges on ribs may be developed as flattened, scale-like spines. Each valve has two small cardinal teeth, and right valve has two anterior and two posterior laterals. Adductor scars and pallial line are distinct. External sculpture is visible as grooves extending from ventral margin. Color of the shell is cream, light yellowish, or pale brown; and periostracum is yellowish or greenish. Inner surfaces are dull white, brown, and thin. It grows to a maximum size of 50 mm and its life span is 7 years. These animals are harvested commercially and eaten in much of its range. Biology Food and feeding: It is a suspension feeder on seston (particulate organic matter). C. edule is able to preferentially select organic particles for ingestion instead of inorganic particles. This species is therefore well adapted to living in turbid environments, such as intertidal mudflats, which are characterized by marked fluctuations in seston quality and quantity, caused by resuspension of fine sediments during periods of high current velocities on the flood or ebb tides (Navarro and Widdows, 1997). Reproduction: In the Northwest Iberian Peninsula, the onset of gametogenesis took place at the end of the summer (September to October) and progressed throughout the winter, and the mature stage was finally reached in spring. The first spawning occurred in April and May, and another spawning took place in May and June. During the summer (July and August), most of the population showed signs of gonad exhaustion, although a less-intensive spawning event was observed at the end of summer and beginning of autumn (Martínez-Castro and Vázquez, 2012). Compound(s) and Activities Antiproliferative and apoptotic activity: The polysaccharides of this species have shown considerable inhibition of cell proliferation with K562 and MOLT4 cell lines with IC50 values 9 µg/mL and 1 µg/mL, respectively (Aldairi et al., 2018).

Tridacna maxima (Röding, 1798)

Order: Cardiida Family: Cardiidae Common name: Common edible cockle

Order: Cardiida

Family: Cardiidae

7

Marine Mollusks

Common name: Small giant clam, maxima clam, elongate giant clam, great clam, rugose clam Distribution: Indo-Pacific: East Africa, India, China, Australia, Southeast Asia, the Red Sea, and the islands of the Pacific Ecology: It is found living in coral reef flats in shallow areas, reef areas of lagoons, and intertidal areas; occupies well-lit areas, due to its symbiotic relationship with photosynthetic algae; and is also found in brackish waters. Depth range 0–35 m. Description: It is less than one-third the size of the true giant clam (Tridacna gigas). Shell colors include combinations of blue, brown, green, gray, purple, and yellow. Patterns can be stripes, blotches, or spots. There are usually larger areas of solid color in this shell. Solid blue maxima clams have been found in the Red Sea. The presence of a prominent row of black pigmented eye spots along the edge of the mantle is the characteristic feature of this species. Mantle color is highly variable, ranging from bright blue to brown. Shells attain a maximum length of 35 cm. Biology Food and feeding: It is a mixotrophic species. It filter feeds and photosynthesizes via its zooxanthellae. Tridacnids derive their nutrition from uptake of dissolved matter through their epidermis and from their symbiotic zooxanthella, Symbiodinium microadriaticum. Reproduction: Sexual maturity of these clams collected from French Polynesia was found to be constant between August and November, 2013, then more variable in the following months. The gonadosomatic index (GSI) was estimated at 0.47 in December 2013, declining to 0.12 in June 2014. The index of male maturity was variable throughout the study period, with no spermatozoid (SPZ) found in the gonads of all giant clams collected in June 2014. In all instances, the male maturity index (SPZ) and the female maturity index (GSI) did not always show synchronic patterns (Wynsberge et al., 2017). Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antibacterial activity: The ethanol and methanol crude extracts of this species exhibited broad antibacterial activity against human pathogenic bacteria. Ethanol extract exhibited highest activity against Staphylococcus aureus (10 mm) and Escherichia coli (7 mm). Aqueous extracts exhibited highest activity against E. coli and Proteus mirabilis. The 10:10 fraction exhibited highest activity against E. coli, Pseudomonas aeruginosa, and S. aureus (Mariappan et al., 2010).

Galatea paradoxa (Born, 1778)

Order: Cardiida Family: Donacidae Common name: Common galatea clam, Volta clam Distribution: Eastern Central Atlantic: Guinea to Congo Ecology: It is a benthic, brackish-water species. Description: This species has two trigonal thick shells with two valves held together by the adductor muscle. Common length of the shell is 9.0 cm. Biology Food and feeding: It is a filter feeder, straining particulate materials from the surrounding water. Reproduction: Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antimicrobial and antioxidant activities: The crude peptide extracted from this species showed antimicrobial activity against eight strains of bacteria (E. coli, S. aureus, Bacillus subtilis, Salmonella typhimurium, Enterococcus faecalis, Klebsiella pneumoniae, Streptococcus pneumoniae, and P. aeruginosa) and one strain of fungi (C. albicans), with MIC values of 17 mg/ml (except for C. albicans, for which the MIC was 20 mg/ml). The zone of inhibition (mm) of extracts of this species against E. coli, S. aureus, S. pneumoniae, P. aeruginosa, and B. subtilis was 20 mm; for S. typhi, E. faecalis, and K. pneumoniae, the values were found to be 15.3, 16.0, and 14.7 mm, respectively. However, the zone of inhibition of this extract for C. albicans was nil. Antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed scavenging ability on the DPPH radical was 56.77% at 0.39 mg/ml for this species. (Borquaye et al., 2015).

Pholas orientalis (Gmelin, 1791)

Tridacna sp. Compound(s) and Activities Antiatherosclerotic activity: The methanolic crude extracts of this unidentified species have shown antiatherosclerotic activities. The effective concentrations were found to be 1.56 μg/ml for diethyl ether fraction and 25.00 μg/ml for butanol fraction (Sarizan, 2013).

Order: Myoida

Family: Pholadidae

8

Common name: Oriental angel wing Distribution: Indo-West Pacific: From Pakistan to Philippines and Indonesia, north to South China Sea and south to Queensland Ecology: It is an intertidal species that burrows in soft mud; depth range 0–20 m. Description: This species has an elongate-ovate inequilateral shell which is longer than it is high and widens towards the umbo. Anterior end is round, and posterior end is narrow. Both anterior and posterior ends are gaping. Anterior and ventral halves of valves are densely ridged and strongly spinose. Posterior and dorsal half of valves are smooth but densely covered with tiny granulations. Ligament is reduced and hinge margin lacks teeth. Three accessory calcareous plates are present along dorsal margins of the valves. Anterior plate is trigonal and elongated, median plate is small and transverse, and posterior plate is long and narrow. Outside of the shell is dirty white. Interior is milky white and porcelaneous. It can attain a maximum length of 12 cm. Biology Food and feeding: It primarily feeds on microalgae and phytoplankton such as Chaetoceros sp., Skeletonema sp., and Isochrysis sp. Reproduction: In its life cycle, there are only three stages; egg, juvenile, and adult stages were identified in the life cycle of this species in three localities in Malaysian waters. In Yan and Lekir, the eggs were found to be released from July to December and from March to August, respectively. In both locations, the eggs developed into juveniles a month after their release. Three months were needed for the juveniles to develop into adults in these two locations. Meanwhile, in Sekinchan, eggs were released from December to January and juveniles were found in January; the adult stage was observed after two months of the juvenile stage. In Sekinchan, it took only four months for the eggs to develop to the adult stage. On the other hand, in Yan and Lekir, it took about five months for the egg to develop to the adult stage (Yusop and Ramli, 2017). Compound(s) and Activities Antifungal activity: Cold methanol and PBS (phosphate buffer saline) extracts of body meat and cold methanol extract of the mantle of this species have shown antifungal activities at 1000 mg/ml dose. Of the three fungal strains tested, Trichoderma sp., a fungus that causes skin dermatitis in humans, exhibited a zone of inhibition. Therefore, the extract of this species could potentially be used as an antifungal agent (Seraspe and Abaracoso, 2014). Angiotensin-converting enzyme (ACE) inhibitory activity: The meat hydrolysate of this species showed ACE inhibitory activity with a half maximal inhibitory concentration (IC50) value of 3.63 mg/ml (Amiza et al., 2017).

Biology and Ecology of Pharmaceutical Marine Mollusks

Mya arenaria (Linnaeus, 1758)

Order: Myoida Family: Myidae Common name: Softshell clam, eastern softshell clam, mud clam, soft clam, long-necked clam, long clam, steamer clam, nanny nose, sand gaper Distribution: Pacific Coast of North America, including Alaska, Canada and the continental United States; Northwest Atlantic; Mediterranean Sea Ecology: It lives buried in mud or sandy mud, sometimes mixed with gravel in intertidal areas; it is tolerant of low salinity (as low as 6%o in Baltic Sea) and quite large changes in salinity and temperature; common in estuaries. Description: This species has a shelflike or spoonlike chondrophore projecting from the hinge plate of the left valve; it has two adductor muscles of similar size, and there are no radial ribs. It has a well-developed, deep pallial sinus. Umbones are only slightly anterior to the middle. Hinge ligament is internal, attached to the chondrophore. Posterior end of the shell is less smoothly rounded than is the anterior, but it is not truncate. Valves may gape slightly at each end, especially the posterior end. Shell is brittle and chalky white or gray outside with light yellow or brownish periostracum and uneven concentric rings. Sphons are light brown with darker tips. It has a maximum length of 17 cm. Biology Food and feeding: Mya arenaria are deeply burrowing suspension-feeding bivalves. Reproduction: In this species, sexual maturity usually set in at a size of 20–50 mm. In most north European waters, there is only one spawning period (during early summer months) for this species, but in some places, there are indications of two separate spawning events, one in spring and one in late summer. Fertilization is external, and larvae are pelagic and planktotrophic for 2–3 weeks. Fecundity is high at 100,000–5 million per female per season, and varies with size and age of the female (Jensen, https​://ww​w.nob​anis.​org/g​lobal​asset​s/spe​ ciesi​nfo/m​/mya-​arena​ria/m​ya-ar​enari​a.pdf​). Predators and association: M. arenaria’s predators include snails, crabs, rays, sharks, flounder, sculpin, ducks, cormorants, gulls, shorebirds, sea otters, and raccoons; while

9

Marine Mollusks

jellyfish, comb jellies, and fish feed on the larvae. Five species of small commensal crabs have been found living inside this species. Compound(s) and Activities Antiviral activity: The unidentified bioactive macromolecules of this species showed inhibition of viral infection (LT-1) at intracellular level. Further, inhibition of tumors in hamsters by adenovirus 12 has also been reported (Dang et al., 2011, 2015).

Mytilus chilensis (Hupé, 1854) (=Mytilus edulis chilensis)

Compound(s) and Activities Antimicrobial activity: The antimicrobial peptide isolated from the gill tissues of this species has shown antimicrobial activity as low as 0.045 µg/µl over reference strains. All fractions enriched with low molecular weight peptides displayed neutralizing growth activity against Gram-positive and Gramnegative bacteria and were 10 times more efficient against fungal pathogens. Considering these results, the industrial waste gills of bivalves may serve as a new source for antimicrobial molecules (Mercado et al., 2005). The hemolymph of this species displayed antibacterial activity against V. alginolyticus (Luna-González et al., 2007).

Mytilus edulis (Linnaeus, 1758)

Order: Mytiloida Family: Mytilidae Common name: Chilean blue mussel, Chilean smooth-shelled mussel Distribution: Southeast Pacific, Southwest Atlantic, and Antarctic Ecology: This epifaunal species is found on soft sandy and muddy bottoms and diverse rocky substrates, including cobbles, and is associated with holdfasts or fronds of brown algae in inner fjords, channels, and exposed areas; brackish; depth range 0–100 m. Description: Shell attains a maximum length of 18.0 cm. No other information is available. Biology Food and feeding: It is a filter feeder on seston and particulate organic matter. Reproduction: In the Falkland Islands, the reproductive development of this species proceeded through early to late spring (September–December), whilst spawning occurred mainly during the southern summer (January–February). Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Parasite: A parasitic association between the green alga Coccomyxa parasitica (Chlorococcales) and this mussel species has been reported from the Falkland Islands. C. parasitica occurred within the soft tissues. Tissues of infested mussels were rather watery and translucent, and the adductor muscle appeared weak and stringy. In the affected mussels, the reproductive output was found to be reduced (Gray et al., 1999).

Order: Mytiloida Family: Mytilidae Common name: Blue mussel, common mussel Distribution: Native to North American Atlantic coast; Atlantic Canada Ecology: It is found in intertidal areas, attached to rocks and other hard substrates by strong (and somewhat elastic) thread-like structures called byssal threads, secreted by byssal glands located in the foot of the mussel. Blue mussels are semi-sessile, having the ability to detach and reattach to a surface, allowing the mollusk to reposition itself relative to the water position. Description: Shape of the shell of this species is triangular and elongate with rounded edges. Shell is smooth with a sculpturing of fine concentric growth lines but no radiating ribs. Shells of this species are purple, blue, or sometimes brown in color, occasionally with radial stripes. Shell shows color polymorphism; in younger specimens, the shell is horn colored, frequently marked with blue and brown rays. Outer surface of the shell is covered by the periostracum, which, as eroded, exposes the colored prismatic calcitic layer. In optimal conditions, this species can grow to 60–80 mm in length within 2 years. Biology Food and feeding: M. edulis is a filter feeder, collecting phytoplankton, detritus, and organic material for food.

10

Reproduction: The reproductive cycle of this species in the lower tidal zone at the island of Helgoland showed that the spawning period extended from the end of April until the end of June at water temperatures between 6° and 14°C. Sex ratio did not differ significantly from 1:1. (Sprung, 1983). Biovector: As mussels filter out contaminants, they are likely to serve as vectors for any water-borne disease or contaminant. Compound(s) and Activities Antithrombotic activity: The enzymatic hydrolysate from water-, salt-, and acid-soluble M. edulis protein showed antithrombotic activity with values of 40.17%, 85.74%, and 82.00% at 5 mg/mL, respectively (Qiao et al., 2018). Anticoagulant activity: A potent anticoagulant oligopeptide has been isolated from the edible parts of this species. This peptide could prolong both the thrombin time and the activated partial thromboplastin time, and it specifically interacts with blood coagulation factors FIX, FX, and FII. Further, this peptide could also inhibit proteolytic activation of FX by the intrinsic FXase and formation of FIIa by a prothrombinase complex in dose-dependent reactions (Jung and Kim, 2009). Antihypertensive activity: The fermented blue mussel sauce (FBMS) showed angiotensin I converting enzyme (ACE) inhibitory activity, and the IC(50) value of FBMS for ACE activity was 1.01 mg/ml. An ACE inhibitory peptide purified from FBMS showed an IC(50) value of 19.34 mg/ml. The purified peptide was evaluated for antihypertensive effect in spontaneously hypertensive rats (SHR) following oral administration. Blood pressure significantly decreased after peptide ingestion. This result suggested that FBMS may have beneficial effects on hypertension (Je et al., 2005). Antioxidant activity: The hydrolysate (obtained through papain hydrolysis) of the mussel protein of this species showed high antioxidant activity. Under the optimal hydrolysis conditions (temperature 65°C, pH 7.0, enzymatic hydrolysis time 3 h, and amount of enzyme 1.0%), the high DPPH radical scavenging activity (28.74) of the total hydrolysate was obtained. The fraction F2 with the highest antioxidant activity was collected from the total hydrolysate, with the reducing power, ·OH and DPPH· scavenging ratio being 0.807, 10.44%, and 31.4% at the concentration of 5 mg/ml (Jung et al., 2005; Qu et al., https://ieeexplore.ieee.org/document/5964116/​). Antibacterial activity: The hemolymph of this species displayed antibacterial activity against V. alginolyticus (LunaGonzález et al., 2007). Anti-Bacillus megaterium activity: The plasma proteins of this species showed strong anti-B. megaterium activity (Anderson and Beaven, 2001). Antimicrobial activity: The peptides from the gill tissues of this species showed antimicrobial activity. All fractions enriched with low molecular weight peptides displayed neutralizing growth activity against Gram-positive and Gramnegative bacteria and were 10 times more efficient against fungal pathogens. Active fractions were found to be thermostable and noncytotoxic to eukaryotic cells. Considering these

Biology and Ecology of Pharmaceutical Marine Mollusks

results, industrial waste gills of these bivalves serves as a new source for antimicrobial molecules (Mercado et al., 2005). The antimicrobial peptides (AMPs) mytilin A and B have been derived from the hemocytes of this species. Mytilin A has antibacterial activity against A. erococcus viridans, B. megaterium, Micrococcus luteus, E. faecalis, S. aureus, and E. coli. It is also active against the marine species A. carrageenovora, P. alginovora, and C. drobachiensis (Anon., http://www.uniprot.org/uniprot/P81612), where mytilin B showed both antibacterial and antiviral activity (Anon., http:// www.uniprot.org/uniprot/P81613).

  Mytilin A Mytilin B Others: Adhesive protein present in byssus of this species is used as adhesive for surgical applications (Ninan et al., 2007).

Mytilus galloprovincialis (Lamarck, 1819)

Order: Mytiloida Family: Mytilidae Common name: Mediterranean mussel Distribution: Europe: Mediterranean Sea and Black Sea, on Atlantic coasts, in Portugal, north to France and British Isles and Norway; European Arctic including northern Norway and Svalbard; northern Pacific: California Ecology: These mussels usually occur in the low intertidal zone of exposed rocky coasts, also growing in dense patches on the sandy-muddy bottoms of brackish lagoons. Biology: It is a smooth-shelled mussel with a slightly broader base. Its two valves are equal and are nearly quadrangular. Mantle edge is darker, becoming blue or purple. Color of the shell is dark blue or brown to almost black. Outside is black-violet colored on one side, and the rim of the shell ends with a pointed and slightly bent umbo while the other side is rounded. Shell attains a maximum length of 15 cm.

11

Marine Mollusks

Biology Food and feeding: It is a filter feeder on phytoplankton and organic matter. Reproduction: This species has gonochoristic reproduction where males and females spawn simultaneously. In Galicia, reproduction of this species may take place at any time of the year. They produce millions of eggs. Fertilization is external. Fertilized eggs develop into a trochophore larvae, and then into a veliger that is carried by tide and currents. When they reach a shell length of 0.25 mm, the pediveligers attach themselves with their byssus threads to filamentous substrates. They are able to detach themselves and reattach to other substrates (FAO, http:​//www​.fao.​org/f​i sher​y/cul​tured​speci​es/My​ tilus​_gall​oprov​incia​lis/e​n). Compound(s) and Activities Cytotoxic activity: The toxic compounds oxazinins 1, 2, 3, and 4 have been derived from the digestive glands of this species. Among them, oxazinin 1 was shown to inhibit the growth of WEHI 164 and J774 cell lines in vitro (Blunt et al., 2016; Ciminiello et al., 2001, 2006).

Myticin A MBC (µM)

Myticin B

  Micrococcus luteus

2.25–4.5

1–2

    Bacillus megaterium

2.25–4.5

1–2

    Staphylococcus aureus

>20 

>20 

    Listeria monocytogenes

>20 

>20 

    Enterococcus viridians

9–4.5

2–4

    Enterococcus faecalis

>20 

NT

    Escherichia coli D31

>20 

120–210

    Salmonella Newport

>20 

120–210

    Salmonella typhimurium

>20 

>20 

    Brucella suis

>20 

>20  >20 

Organism Bacteria: Gram‐Positive

Bacteria: Gram‐Negative

    Pseudomonas aeruginosa

>20 

    Enteromonas aerogenes

>20 

NT

    Vibrio alginolyticus

>20 

NT

    Vibrio vulnificus

>20 

>20 

    Vibrio splendidus

>20 

>20 

>20 

5–10

>20 

>20 

>20 

Fungus   Fusarium oxysporum Protozoan   Perkinsus marinus

 

Mayer and Hamann (2002) also reported that the myticins A and B had marked activity against the Gram-positive strains M. luteus, Bacillus megaterium, and Enterococcus viridians. The antimicrobial peptide mytilin B has also been isolated from this species (Anon., http://www.uniprot.org/uniprot/ Q9Y0B1). Antiviral and antibacterial activities: The C10C-designed   peptide from the compound mytilin of this species showed Oxazinin 3 Oxazinin 4 both antibacterial and antiviral properties. An inhibition of 50% was obtained by in-vitro pre-incubation of white spot syndrome virus (WSSV) with 45 μM of C10C compared with Hubert et al. (1996) reported that the plasma of this species 7 μM for mytilin. C10C was also capable of inhibiting in-vitro contains cytotoxic activity against both vertebrate (erythrogrowth of Vibrio splendidus LGP32 (MIC 125 μM), Vibrio cyte and mouse tumor) and protozoan cells. anguillarum (MIC 2 mM), Micrococcus lysodeikticus, and E. Antioxidant and anti‐inflammatory activities: Among the coli (MIC 1 mM) (Roch et al., 2008). multifunctional bioactive peptides (produced by gastrointesAntiviral activity: The myticin C peptides extracted from tinal digestion) isolated from this species, the 28°C). The female:male ratio was 1:1.3, and no hermaphrodites were detected (Duran et al., 2013). Parasite: Burrowing polychate worm Polydora sp. was found to infest this culturable mollusk, causing problems for production and marketing (Tinoco-Orta and Cáceres-Martı ́nez, 2003). Compound(s) and Activities Antiproliferative activity: The protein extracts (3F3 and 2F2) of this species showed an antiproliferative effect against HeLa and MDA-MB-231 cell lines. The extract 3F3 showed IC50 values of 138.035 and 157.19 µg/ml, respectively, and 2F2 showed IC50 values of 67.46 µg/ml on HeLa cells (García-Morales et al., 2016).

Cyclina sinensis (Gmelin, 1791)

striae. Surface is covered with nidus and fawn-colored epidermis with a beautiful violet band near the border. Of the three cardinals in the right valve, the middle is the stoutest, the anterior one is shortest and thin, and the largest or posterior one is slightly arched and bifid. In the left valve, the posterior is longest and thin, while the middle and anterior ones are slightly bifid. Shell has maximum length of 5 cm. Biology Food and feeding: It is a suspension-feeding bivalve and it feeds on phytoplankton, benthic microalgae, macroalgae detritus, and bacteria. Reproduction: This clam is dioecious and oviparous. On the west coast of Korea, its spawning period was found to be between early July and September, and the main spawning occurred between July and August when the sea-water temperature was over 20°C. The reproductive cycle of this species can be divided into five successive stages: early active stage (February–April), late active stage (March–June), ripe stage (April–August), partially spawned stage (July– October), and spent/inactive stage (September–February). Percentages of first sexual maturity of female and male clams measuring 26.1–30.0 mm in shell length were 53.3% and 62.5%, respectively; and 100% for the clams > 41.0 mm. It is assumed that both sexes begin reproduction at about two years of age (Kim et al., 2000). Compound(s) and Activities Antioxidant and hepatoprotective activities: The polysaccharides isolated from this species had potent antioxidant and hepatoprotective activities (Jiang et al., 2013). Treatment for lung infection: Powder of this species is used to clear heat in the lungs and resolve phlegm (Wu et al., 2014). Antibacterial activity: The peptide isolated from this species showed antibacterial activity (Anon., http://www.uniprot. org/uniprot/U3KTS1). Others: A Kazal-type serine protease inhibitor homolog gene (designated as CsKPI) has been identified from this species. In humans, the protease inhibitor has been reported to regulate the functions of proteases involved in the body’s response to injury (Ren et al., 2015).

Gafrarium divaricatum (Gmelin, 1791)

Order: Veneroida Family: Veneridae Common name: Chinese venus, black clam, iron clam, Korean cyclina clam, Oriental cyclina, venus clam Distribution: Indo-West Pacific; coast of seas in East Asia, such as the Yellow Sea and East Sea Ecology: This benthic species occurs in intertidal areas of sand and mud; depth range 0–50 m. Description: Shell sculpture of this species consists of both concentric and irregular striations, which are somewhat raised over the surface and become more elevated towards the extremity, and they are crossed with fine impressed radiating

Order: Veneroida Family: Veneridae Common name: Forked venus Distribution: Indo-West Pacific: from East and South Africa to the Philippines; north to Japan and south to Malaysia

36

Biology and Ecology of Pharmaceutical Marine Mollusks

Ecology: It is found in intertidal areas in coarse sand and gravel; depth range 0–20 m. Description: Shell of this species is thick, rounded, ovate, and compressed; lunule is shallow; umbo is slightly anterior; beak is pointing slightly to the anterior; outer shell surface is variable in color, usually white or tan, with variable patterns of dark or light brown pigmentation; inner shell surface is white in color, with a posterior purple ray; three cardinal teeth are seen on each valve; and pallial sinus is absent. Size of the shell varies from 3.4 to 4.5 cm in length.

Anticancer/antitumor activity: The crude methanolic extract of this species showed anticancer/antitumor properties, and the compounds responsible for this activity are octadecane, 2,2,4​,15,1​7,17-​hexam​ethyl​-7,12​-bis(​3,5,5​-trim​ethyl​ hexyl​) and L-ascorbic acid 2,6-dihexadecanoate (Babar et al., 2016).

Biology Food and feeding: Like many other bivalves, venus clams are filter feeders. They lie buried in the sand and extend their siphons to the surface at high tide. They use their siphons to suck in water and filter out microscopic food. Reproduction: Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antimicrobial activity: The crude methanolic extract of this species showed consistent antimicrobial activity against Cryptococcus neoformans, Aspergillus flavus, and Aspergillus niger, with minimum inhibitory concentration (MIC) of 0.1, 0.3, and 0.3 mg/ml, respectively. The compounds isolated from this extract with the antimicrobial properties include L-Ascorbic acid 2,6-dihexadecanoate; 2-Cyclopentene-1tridecanoic acid; and 17-(1​,5-Di​methy​lhexy​l)-10​,13-d​imeth​ yl-2,​3,4,7​,8,9,​10,11​,12,1​3,14,​15,16​,17-t​etrad​ecahy​d ro-1​H-cyc​ lopen​ta[a]​phena​nthre​n-3-o​l (Babar et al., 2016).

L-Ascorbic acid 2,6-dihexadecanoate

2-Cyclopentene-1-tridecanoic acid

17-(1​,5-Di​methy​lhexy​l)-10​,13-d​imeth​yl-2,​3,4,7​,8,9,​10,11​,12,1​ 3,14,​15,16​,17-t​etrad​e cahy​d ro-1​H-cyc​lopen​t a[a]​phena​nthre​ n-3-o​l

octadecane, 2,2,4​,15,1​7,17-​hexam​ethyl​-7,12​-bis(​3,5,5​-trim​ ethyl​hexyl​)

Marcia opima (Gmelin, 1791)

Order: Veneroida Family: Veneridae Common name: Venus shell, fertile venus, baby clam Distribution: Indo-Pacific: from northwest Indian Ocean and the Aden Gulf to Indonesia Ecology: This benthic species is primarily marine but is also found in brackish waters; invades backwaters and estuaries; is found in protected coastal areas, with shallow subtidal waters; and is found in muddy and sandy substrates, where it burrows; depth range 0–20 m. Description: Shell of this species is small, thick, solid, and flattened, with a glossy surface. It is covered by a thin periostracum in live conditions. Umbo curves towards the anterior (prosogyrate). Prominent and deeply depressed lunule is present. Fine concentric striations are present on the shell surface. The yellowish brown or straw-colored shell is spotted and rayed with undulating concentric purplish grey markings. Between three and four radial bands radiate from the umbo. Inner surface of the shell is white. Hinge plate has three teeth.

37

Marine Mollusks

Anterior lateral teeth are absent in left valve but there is a corresponding depression present on right valve. Shell of this species grows to a maximum length of 6.5 cm. Reported age of this species is 3 years. Biology Food and feeding: It is a suspension feeder, filtering planktonic algae and organic matter from the water. Reproduction: The reproductive cycle of this species was studied at two sites along the southeast (Tuticorin Bay) and southwest (Ashtamudi estuary) coast of India. Both sites showed two spawning seasons. On the southeast coast, the first spawning season was recorded from May to July. On the southwest coast, the first spawning season was observed from March to May. A second spawning season from September to December was recorded on both coasts. Most of the animals were either in the spent or indeterminate gonadal stage from May to August and November to January, indicating the active spawning during those months on the southeast coast (Suja and Muthiah, 2007). Compound(s) and Activities Anticoagulant activity: The glycosaminoglycans (GAGs) of this species exhibited prominent anticoagulant activity (Pandian and Thirugnanasambandan, 2008).

Mercenaria campechiensis (Gmelin, 1791)

Biology Food and feeding: It is a filter feeder, sieving microscopic plankton (mainly diatoms and other microalgae) from the water column. When buried in the sand, the clam extends two siphons above the surface of the sediment. The incurrent siphon imports food and dissolved oxygen from the surrounding water column, while the excurrent siphon expels waste. Reproduction: It is a protandrous hermaphrodite, with about 98% of individuals beginning life as males and changing to females as they grow older. It reproduces via external fertilization, releasing gametes into the water column. Spawning occurs in warmer months during neap tides. After fertilization, larvae pass through three main planktonic stages before developing into settled, juvenile clams. The first is the trochophore stage, which is formed 12–14 hours following fertilization. After 1 day, larvae enter the veliger stage, growing lobes or paddles that resemble butterfly wings. During this stage, the shell and internal organs develop. After about 10 days, larvae develop a foot and are termed pediveligers. These veligers find suitable substratum for settlement (Anon., https:// www.sms.si.edu/irlspec/Mercen_campec.htm).​ Compound(s) and Activities Anticancer activity: The mercenene isolated from this species showed both in-vivo and in-vitro inhibitory activity against Hela cells, which were completely degenerated within 72 hours. This compound was also effective against virusinduced leukemia mice, although the infected mice all died eventually (Maramorosch, 2012; Schmeer and Beery, 1965).

Mercenene

Mercenaria mercenaria (Linnaeus, 1758) Order: Veneroida Family: Veneridae Common name: Southern quahog, southern hard clam Distribution: Western Central Atlantic: from Chesapeake Bay to Florida, Texas and the Yucatán Peninsula to Cuba Ecology: It is found from intertidal sand flats to offshore depths of up to 40 m. Description: Heavy shell of this species is ovate, trigonal, and inflated, with valves of equal size. Several concentric growth lines are present on the gray-to-whitish exterior. Three cardinal teeth (the middle one split) on each valve help to hold the shell together at the hinge. External shell color is dull white to gray. Interior color of the shell is often porcelaneous white, with purple marks occurring rarely. Two muscle scars are present on the interior surface, both attached to the pallial line.

Order: Veneroida Family: Veneridae Common name: Northern quahog, hard clam, cherrystone, littleneck, hard-shell clam

38

Distribution: From the gulf of St. Lawrence, along the east coast of the United States, around the Florida peninsula and into the Gulf coast of Texas Ecology: It is found buried in muddy sediment on the lower shore and shallow sublittoral and in bays and estuaries; it prefers sandy environments to depths of 15 m. Description: It has a large, heavy shell that ranges from being a pale brownish color to shades of gray and white. Exterior of the shell, except nearest the umbo, is covered with a series of growth rings. Interior of the shell is colored a deep purple around the posterior edge and hinge. It has a maximum length of 13.0 cm and its maximum reported age is 9 yrs. Biology Food and feeding: It is a filter feeder, sieving microscopic plankton (mainly diatoms and other microalgae) from the water column. Reproduction: It is a protandric hermaphrodite, with the male developing first. In the Indian River Lagoon, spawning occurs in the autumn after water temperatures drop below 23°C. Fertilized eggs become trochophore larvae within the first 12 hours; shells develop within 26–30 hours. The veliger stage is reached in another 8–12 hours. Veligers are planktonic for approximately 12–14 days before settling. With settlement, its velum disappears and the foot of this species is mainly used for burrowing and crawling (Anon., Indian River Lagoon Species Inventory. https​://ww​w.sms​.si.e​du/ir​lspec​/ Merc​en_me​rcen.​htm).​ Compound(s) and Activities Antiviral activity: The organic extracts of this species containing unidentified bioactive macromolecules have shown antiviral activity (Dang et al., 2011, 2015). Anticancer/antitumor activity: The compound mercenene isolated from this species was inhibitory for sarconema 180 and the Krebs-2 carcinoma in Swiss mice. It was also effective against virus-induced leukemiai mice, although the infected mice all died eventually (Maramorosch, 2012). Li et al. (1972) reported that the aqueous extracts of this species displayed activity against adenovirus 12 and SV40 virus-induced tumors in hamsters. Half of 74 treated hamsters showed complete tumor regression within 4 weeks after the first injection. A limited number of melanomas in CDF1 mice were similarly treated with clam extract, and one-third showed complete regression. Anticoagulant activity: The heparin (3-O-sulfated GlcNAc residues) isolated from this species showed increased anticoagulant activity with 348 USP units/mg (Jordan and Marcum, 1986; Pavão and Mourão, 2012). Antibacterial activity: The organic extracts of this species have shown antibacterial activity (Różańska et al., 2012).

Biology and Ecology of Pharmaceutical Marine Mollusks

Meretrix casta (Chemnitz, 1782)

Order: Veneroida Family: Veneridae Common name: Yellow clam, backwater hard clam Distribution: Indo-West Pacific Ecology: It is a benthic and brackish-water species found burrowing in estuarine, backwater, and subtidal habitats; depth range 0–6 m. Description: It has an ovate shell with a thick and horny periostracum. Anterior and posterior lateral teeth are present. Posterior lateral tooth is long. There is an elongate and strong hinge and a shallow pallial sinus. Outer surface of the shell is covered by periastracum, which, as it erodes, exposes the yellow color. It attains a maximum length of 7.5 cm. Biology Food and feeding: It is a suspension feeder, mainly depending on phytoplankton and detritus material for its nutrition. Reproduction: It is a protandric hermaphrodite. In the estuaries of Kerala, India, females of this species became mature in June and October. Males with maturing gonads appeared during January, March, June, October, and December. Spawning occurs throughout the year, with peak spawning in March–April and August–September (Laxmilatha et al., 2006). Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antibacterial activity: The whole body extracts of this species displayed antibacterial activity against human pathogenic bacteria. Highest activity was exhibited against E. coli (8 mm) and S. typhi (8 mm) by the crude extract of ethanol. Aqueous extracts exhibited highest activity against E. coli and P. mirabilis. The 10:10 (methanol: ethanol) extracts of this species showed highest activity against P. mirabilis (8 mm); and 14:6, 4:16, and 2:18 fractions showed higher activity against P. aeruginosa, E. coli, and K. pneumoniae. The 18:2, 12:8, and 2:18 fractionated extracts showed highest activity against S. aureus, S. typhi, and E. coli (Mariappan et al., 2010).

39

Marine Mollusks

Pachaiyappan et al. (2014b) reported that the crude extracts of this species exhibited significant antibacterial activity. Among the six samples tested, acidic extraction (Ax) exhibited highest activity against the tested human pathogens, specifically against S. pneumonia (10 mm). The other solvent extracts Hx, can, and Ch also exhibited effective antibacterial activity against the following: K. pneumoniae (5.5 mm), S. aureus (4 mm), S. pneumoniae (10 mm), E. coli (4 mm), Vibrio parahemolyticus (8 mm), S. typhi (2 mm), Klebsiella oxytoca (9. 7 mm), P. mirabilis (7 mm), V. cholerae (5 mm), and S. paratyphi (2 mm). Antioxidant activity: The protein hydrolysate isolated from this species and its crude methanolic extracts showed antioxidant activity (Nazeer et al., 2013; Pachaiyappan et al., 2014a). Anticoagulant activity: The crude extracts of this species showed anticoagulant activity with the following values: sheep blood 22.52 USP units/mg; chicken blood 20.00 USP units/mg; and human blood 18.60 USP units/mg (Periyasamy et al., 2013). Antiangiogenic activity: The methanolic extract of this species exhibited noticeable antiangiogenic activity at the tested concentration of 200 μg, whereby it significantly inhibited the vascular endothelial growth factor (VEGF)-induced proliferation of new blood vessels (Gupta et al., 2014).

Reproduction: It is a protandric hermaphrodite. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Anticancer activity: The ethyl acetate extract of this species showed anticancer activity, and the compounds showing strong apoptosis-inducing activity were identified as epidioxysterols (Pan et al., 2006). The epidioxysterols have also been reported to induce apoptosis in HL-60 cells showing its potential for treating liver disease and hepatitis as well (Kim, 2012).

Meretrix meretrix (Linnaeus, 1758)

Meretrix lusoria (Roeding, 1798)

Order: Veneroida Family: Veneridae Common name: Asian hard clam, common orient clam, poker chip venus Distribution: It is native to Asia; Northwest Pacific: from Thailand to Japan and Indonesia Ecology: This benthic species tolerates both freshwater and coastal waters; silty sand in tidal flats and subtidal zone; depth range 0–20 m. Description: It attains a maximum length of 5 cm. No other information is available. Biology Food and feeding: As in other Meretrix spp.

Order: Veneroida Family: Veneridae Common name: Asiatic hard clam, yellow clam Distribution: Indo-West Pacific: from East Africa to the Philippines; north to Japan and south to Indonesia Ecology: This benthic species is found in sand and muddysand bottoms of intertidal and areas in sand and mud; also in estuaries and backwaters; depth range 0–20 m. Description: Shell of this species is strong, glossy, triangularly ovate, and inflated, covered by thin, transparent, fine straw-colored periostracum. Dorsal margin slopes strongly on both sides. Anterior and posterior edges are rounded. Lunule is indistinct and smooth. It is a smooth shell with faint concentric growth marks. Umbones are prosogyrate, large, and inflated. Hinge plate is thick with three cardinal teeth. Stout, distinctly notched anterolateral tooth is seen in left valve. Pallial sinus is shallow and feebly developed. Internal margins are smooth. Outer shell is white with a purplish tinge on the dorsal slope. Interior is white with brown posterodorsal slope. Shell attains a maximum length of 7 cm. Biology Food and feeding: It is a filter feeder on particulate organic matter. Reproduction: It is a gonochoric and protandric hermaphrodite. In the intertidal zone of Nam Dinh province (Vietnam), the

40

Biology and Ecology of Pharmaceutical Marine Mollusks

reproductive cycle of this species involved five stages: proliferation stage, growing stage, maturation stage, breeding stage, and suspensive stage. When sexually mature, gonads of females are light brown and those of males are milky white. The spawning season was from late April to early September and the peak of spawning occurred from mid-May to late July. During the spawning season, the sex ratio (male:female) was 0.98:1.11. First sexual maturity occurred at a length of 40 mm. Fecundity ranged from 318,400 to 3,825,000 eggs/individual. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antioxidative capacity: The crude methanolic extracts of this species showed maximum 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with 74.52% (Pachaiyappan et al., 2014a). Antiangiogenic activity: In the chick chorioallantoic membrane assay, the methanolic extracts of this species exhibited noticeable antiangiogenic activity at the concentration of 200 μg. These extracts significantly inhibited the VEGF-induced proliferation of new blood vessels with an inhibitory percentage of 47.01 (Gupta et al., 2014). Immunological activity: The water-soluble polysaccharide MMPX-B2 isolated from this species was found to stimulate the murine macrophages to release various cytokines (Li et al., 2016). Antitumor/cytotoxic activity: A novel protein from the coelomic fluid of this species exhibited significant cytotoxicity to several cancer cell types, including human hepatoma BEL-7402, human breast cancer MCF-7, and human colon cancer HCT116 cells (Ning et al., 2009). A linear (novel) polypeptide isolated from this species exhibited in-vivo activity against the growth of a human lung adenocarcinoma A549 xenograft in nude mice in a dosedependent manner. This compound was also able to induce cell cycle arrest in G2/M phase followed by apoptosis. This apoptosis was characterized by the cleavage of procaspases 9 and 3, membrane blebbing, loss of mitochondrial membrane potential with subsequent Cyt C release, externalization of phosphatidylserine, condensation of chromosomes, and fragmentation of DNA (Ruiz-Torres et al., 2017). MGP0501, a low-molecular-weight glycopeptide extracted from this species, exhibited a stable and broad spectrum antitumor activity in Institute of Cancer Research (ICR) mice against xenografted sarcoma 180 (S180), Hepatocellular carcinoma (Heps) and Ehrlich’s ascitic carcinoma (EAC) (Wu and Xu, 2015).

Effect of MGP0501 on Heps in Mice Dose (mg/kg)

Inhibitory Rate (%)

2.0

58.0

0.6

49.7

Source:  Wu and Xu (2015).

Life Elongation Effect of MGP0501 on EAC Mice Dose (mg/kg)

Life Elongation Rate (%)

2.0

8.3

0.6

3.8

Source:  Wu and Xu (2015).

Meretrix petechialis (Lamarck, 1818)

Order: Veneroida Family: Veneridae Common name: Spotted hard clam Distribution: Northwest Pacific: west coast of the Korean Peninsula, Japan, and China Ecology: This benthic species lives in sheltered muddy and sandy tidal flats; depth range 0–20 m. Description: M. petechialis is considered to be the closest relative of M. lusoria. Shell shape of this species is suboval. Its posterior dorsal margin is quite swollen. Coloration of the shell is yellowish-brown or white, often with irregular brown and brown bands and the inner surface of the shell is white. It attains a maximum length of 7 cm. Biology Food and feeding: As in other Meretrix spp. Reproduction: In Japan, this species matures during summer, and mass spawning occurs from August to September. It possess a pelagic larval dispersal phase of various lengths that allows movement away from home habitats. The length of the pelagic veliger larval phase in this species is 2–3 weeks (Yamakawa and Imai, 2012). Compound(s) and Activities Anti-HIV activity: A new polysaccharide composed of galactan sulfate with a β-(1→3)-glycosidic linkage isolated from this species displayed anti-HIV activity. The polysaccharide was homogeneous in its composition, containing d-galactose. The anti-HIV activity of the polysaccharides has been evaluated by the inhibition of syncytia formation. The fusion index and percentage fusion inhibition of sulfated galactan were 0.34% and 56% at 200 μg/mL (Amornrut et al., 1999).

41

Marine Mollusks

The sulfated b-galactan of this species exhibited in-vitro syncytia inhibition of HIV binding to CD4 (Mayer and Hamann, 2002).

Protapes gallus (Gmelin, 1791)

Paratapes undulatus (Born, 1778)

Order: Veneroida Family: Veneridae Common name: Undulate venus, undulated surf clam, yellow clam, baby clam, short-necked clam, carpet shell clam Distribution: Indo-West Pacific: Red Sea, to Papua New Guinea; north to Japan and south to New South Wales Ecology: This benthic species inhabits inshore shallow sandy seabed; Intertidal to sublittoral; depth range 0–50 m. Description: Shell of this species is egg-shaped, brownish, thin, and symmetrical between upper and lower halves of shell. Periostracum of the shell has wax-like appearance. A dark-brownish net pattern covers the entire periostracum. Interior of the shell is white in color. It reaches a length of 6.5 cm. Biology Food and feeding: It is a suspension feeder and its diet includes planktonic organisms, suspended solids and other microorganisms. Reproduction: Fertilized eggs develop into a swimming blastula stage in 2:30 h. Trochophore stage appears after 5 hours of fertilization. A D-shape stage and an umbo stage appear after 12 h and 120 h respectively. The pediveliger stage (foot is developed for crawling onto seabed) and the spat appear after 8 days and 12 days, respectively (Chanrachkij, 2013). Compound(s) and Activities Hepatoprotective activity: The bioactive compounds, namely, the hydrolysates, isolated from this species have shown potential hepatoprotective roles through antioxidant activities (Nair et al., 2015). Others: Its eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be of great use in the development of functional foods for preventing cardiovascular diseases (Cheng et al., 2009).

Order: Veneroida Family: Veneridae Common name: Rooster venus Distribution: Indo-West Pacific: from western India to Papua New Guinea; north to Taiwan Province of China and the south China Sea, and south to New South Wales Ecology: This benthic species is found in intertidal areas in sand and mud; depth range 0–50 m. Description: Shell of this species is thick, heavy, and inflated with prominent umbones that point forward. It is beige in color with concentric reddish brown zones. Anterior margin is more rounded and narrower than rear. Posterior margin is truncated and has an angular keel. Regularly spaced, broad, and flattened concentric ridges have narrow grooves between them. Coarse concentric ribs with well-incised grooves cover the entire shell. Cardinal teeth are well developed. Pallial sinus is deep. It attains a maximum length of 7.5 cm. Biology Food and feeding: Like many other bivalves, venus clams are filter feeders. They lie buried in the sand and extend their siphons to the surface at high tide. They use their siphons to suck in water and filter out microscopic food. Reproduction: It is a protandric hermaphrodite. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam. Compound(s) and Activities Antioxidant activity: The organic extracts of this species showed antioxidant activity. The scavenging potential of 2,2-diphenyl-2-picryl-hydrazyl radical and reducing action of this species increased in a dose-dependent manner. Inhibition of lipid peroxidation shown by methanol extract and its significant correlation with OH-scavenging activity implies its potential to protect the cells from damage by reactive oxygen species (Pawar et al., 2013). Antihypertensive, anti-inflammatory, and antidiabetic activities: This species may serve as a potential source of functional food supplements to treat free-radical-induced diseases, such as inflammation, diabetes, and hypertension (Joy et al., 2016).

42

Ruditapes decussatus (Linnaeus, 1758)

Order: Veneroida Family: Veneridae Common name: Grooved carpet shell, Palourde clam Distribution: Atlantic coast of the Iberian Peninsula and of the Mediterranean basin, as well as Ireland Ecology: It occurs at lagoonal and coastal sites. Description: Shell of this species is broadly oval to quadrate, with the umbones distinctly anterior. Posterior hinge line is straight, posterior margin is truncate, and anterior hinge line grades into the down-sloping anterior margin. Shell surface has a sculpture of fine concentric striae and bolder radiating lines. Each valve has three cardinal teeth: the center one is in the left valve, and center and posterior in right are bifid. Pallial line and adductor scars are distinct. Pallial sinus is U-shaped, not extending beyond the midline of the shell but reaching a point below the posterior part of the ligament. Lower limb of the sinus is distinct from the pallial line for the whole of its length. Inner surfaces of the shell are glossy white, often with yellow or orange tints, and with a bluish tinge along the dorsal edge. The overall color of the shell is cream, yellowish, or light brown, often with darker markings. This species has ecological and economic interest as it has been proposed as a bioindicator. Biology Food and feeding: It filters water through its two siphons (one in and the other out), catching organic matter (detritus) and phytoplankton as food. Reproduction: Its sexes are separate, although hermaphrodites can occasionally be found. Fertilization is external and takes places mainly during summer. The larvae swim freely for 10–15 days before settling as spat of about 0.5 mm on a sand and silty mud substrate. Compound(s) and Activities Antimicrobial activity: The antimicrobial peptides, viz. mytilins (isoform A and B) and myticins 1–3, of this species showed potent bactericidal activity against several Grampositive bacteria (M. lysodeikticus, B. megaterium, and Enterococcus viridans) (Li et al., 2011).

Biology and Ecology of Pharmaceutical Marine Mollusks

Ruditapes philippinarum (Adams and Reeve, 1850) (=Tapes (Ruditapes) philippinarum)

Order: Venerida Family: Veneridae Common name: Manila clam, Japanese littleneck clam, Japanese cockle, and Japanese carpet shell Distribution: Coasts of the Indian, Philippines and Pacific Oceans from Pakistan and India north to China, Japan, and the Kuril Islands Ecology: It is found in shallow waters in substrates of coarse sand, mud, and gravel; littoral and sublittoral zones; and brackish waters and estuaries; burrows no more than about 10 centimeters into the substrate; sometimes lives in eelgrass beds. Description: Shell of this species is solid, equivalve, and inequilateral and beaks in the anterior half. It is somewhat broadly oval in outline. Ligament is inset, not concealed. Lunule is elongate and heart-shaped, with light and dark brown fine radiating ridges. Sculpture is of radiating ribs and concentric grooves, the latter becoming particularly sharp over the anterior and posterior parts of the shell, making the surface pronounced decussate. Three cardinal teeth are seen in each valve. Pallial sinus is relatively deep, though not extending beyond the center of the shell, and it leaves a wedge-shaped space between its lower limb and the pallial line. Margins are smooth. Shell is extremely variable in color and pattern: white, yellow, or light brown, sometimes with rays, steaks, blotches, or zig-zags of a darker brown, slightly polished; and inside of shell is polished white with an orange tint, sometimes with purple over a wide area below the umbones. Shell length of fishable size is 3 cm. Biology Food and feeding: It is a filter feeder on particulate organic matter (including phytoplankton and microphytobenthos) present in water column and sediment. Reproduction: It is strictly a gonochoric species. The period of reproduction varies according to the geographical area; spawning usually occurs between 20–25°C. A period of sexual rest is observed from late autumn to early winter. Gametogenesis in the wild lasts 2–5 months, followed by spawning. A second spawning event may occur in the same season, 2–3 months later. Larval development lasts 2–4 weeks

43

Marine Mollusks

before spat fall. Settlement size is between 190 and 235 µm in shell length. The larvae settle by attaching a byssus to a pebble or piece of shell (FAO, http:​//www​.fao.​org/f​isher​y/cul​ tured​speci​es/Ru​ditap​es_ph​ilipp​inaru​m /en)​. Compound(s) and Activities Antiviral activity: The organic extracts of this species showed antiviral activity (Dang et al., 2015). Anticancer activity: A novel anticancer peptide has been purified from the hydrolysates of this species. This peptide effectively induced apoptosis on prostate, breast, and lung cancer cells (Kim et al., 2013). Anti-inflammatory activity: The water extract of this species containing the active compound taurine has shown antiinflammatory effects (Cheong et al., 2015). Anticoagulant activity: The heparin [IdoA2S-GlcNS,6S] isolated from this species was found to be identical to that of human and porcine intestinal mucosal heparins and bovine intestinal mucosal heparin. It showed increased anticoagulant activity with 350 USP units/mg in comparison with pharmaceutical bovine mucosal heparin (Pavão and Mourão, 2012; Luppi et al., 2005). Others: The desmosterol and other sterols viz. 22-trans24-norcholesta-5,22-dien-3β-ol, 22-dehydrocholesterol, cholesterol, brassicasterol, desmosterol, campesterol, 24-methylenecholesterol, stigmasterol and β-sitosterol have been isolated from this specs (Teshima et al., 1971). These sterol compounds regulate biological processes and sustain the domain structure of cell membranes, where they are considered to be membrane reinforcers.

 

Desmosterol         Campesterol

 

24-methylenecholesterol      Stigmasterol

β-sitosterol

Sunetta scripta (Linnaeus, 1758)

22-tr​ans-2​4-nor​chole​sta-5​, 22-d​ien-3​β-ol

​22-de​hydro​chole​stero​l

 

Cholesterol          Brassicasterol

Order: Venerida Family: Veneridae. Common name: No common names found Distribution: East and west coasts of India Ecology: It has a shallow burrowing habit. Description: Shell of this species is wedge shaped; umbo is posterior; beak is seen slightly in front of midlines; anterior end is rounded and posterior is truncated; sculpture is only in the form of growth lines. Color pattern of the shell is white or beige, lilac with brown-violet zig-zag lines or with deep violet patches; and inner ventral margin is crenulated. Shell length varies from 1.9 to 3.8 mm.

44

Biology and Ecology of Pharmaceutical Marine Mollusks

Biology Food and feeding: It is a suspension feeder on particulate matter, including phytoplankton. Reproduction: Individuals collected from Cochin (India) showed a sex ratio of 1:1. First sexual maturity was observed within the first year of life, when the shell length was greater than 22 mm. Spawning in females was observed from October to March (Katticaran, 1988).

Compound(s) and Activities Anticoagulant activity: Heparin (GlcA-GlcNS,6S) sulfated polysaccharides isolated from this species showed high anticoagulant activity with 180 USP units/mg. A large portion of the polysaccharide chain of this species showed high affinity to immobilized antithrombin (Pejler et al., 1987; Pavão and Mourão, 2012).

Compound(s) and Activities Antimicrobial activity: The peptide sunettin isolated from this species showed antimicrobial activity (Sathyan et al., 2012).

2.2 CLASS: GASTROPODA Cellana grata (Gould, 1859)

Tivela mactroides (Born, 1778)

Order: Veneroida Family: Veneridae Common name: Trigonal tivela Distribution: Western Central and Southern Atlantic: from Guatemala to Cuba in the Caribbean; east to Ascension Island; and south to Santa Catarina Brazil Ecology: This benthic species lives in sand, from intertidal areas to very shallow subtidal depths; shallowly buried in sandy bottoms; abundant near river mouths where organic matter and terrigenous particulates accumulate; depth range 0–2 m. Description: Shell of this species is heavy, thick, inflated, and triangular. Umbones are central and prominent. Hinge has three cardinal teeth, and smaller secondary teeth are also present. Lateral tooth in left valve is large. Lunula is large. Periostracum is like varnish. Color of the shell is whitish with brown tinges and rays. It attains a maximum length of 3.4 cm. Biology Food and feeding: It is a suspension feeder. Reproduction: On the southeast coast of Brazil, this species had heterogeneous continuous gametogenesis with no resting period, and the sex ratio did not differ significantly from 1:1. A high proportion of spawning was observed in winter and spring; however, small releases of gametes may also have occurred during summer and autumn. It is a protandric hermaphrodite. Embryos develop into free-swimming trocophore larvae, succeeded by the bivalve veliger, resembling a miniature clam.

Phylum: Mollusca Class: Gastropoda Order: Patellogastropoda Family: Nacellidae Common name: Japanese grata limpet Distribution: Western Pacific; off the coast of Japan to Vietnam. Ecology: This benthic, high-zoned species occurs on exposed rocky shores. Description: C. grata reaches a maximum length of 5.6 cm and it has a lifespan of 3 years. Biology Food and feeding: It feeds on epilithic biofilm (organisms attached to rocks). Reproduction: This species has one winter breeding season each year, which can be correlated with major seasonal climatic and hydro-logical events, for example, winter reduction in temperature and higher seas. Its gonadal cycles are likely geared to temperature and food supply. In this species, spawning occurred between November and December, when wave heights are typically 1 m higher than in summer (Liu, 1994). Compound(s) and Activities C24 unsaturated fatty acids: In the female gonad lipids from this species, C24 unsaturated fatty acids such as 5,9–24:2, 9,15–24:2, 5,9,15–24:3, 5,9,17–24:3, 9,17–24:2, 9,15,18–24:3, 5,9,15,18–24:4, and 5,9,15,18,21–24:5 have been isolated. These fatty acids are of great use in human health. However, detailed research is needed on these compounds (Kawashima and Ohnishi, 2006; Blunt et al., 2016).

45

Marine Mollusks

Cellana radiata (Born, 1778)

Order: Patellogastropoda Family: Nacellidae Common name: Rayed wheel limpet Distribution: Indo-Pacific, mainly Australia; Central Pacific Ecology: This benthic species is found on intertidal rocky shores (in littoral and sublittoral areas); depth range 0–2 m. Description: Shell of this species is moderate in size and has numerous, rather flat, granular ridges of varying height. Color of the shell is grayish white to dark brown, with the ribs being somewhat darker. Interior is pale white and iridescent. Markings of the muscles contrast with a dark gray color. Height of the flattened shell varies between 13 mm and 45 mm. It has a life span of 4 years. Biology Food and feeding: As for C. grata Reproduction: In this species, the sexes are uniformly distributed throughout all size groups. The gonads develop from February to May, and spawning begins in June and extends to February or March. Peak spawning periods are from June to August and December to February. High wind speed under optimum conditions of temperature and salinity appears to induce spawning in the animals (Rao, 1973). Compound(s) and Activities Antibacterial activity: The methanol and ethyl acetate extracts of the wet and dry whole animal of this species have shown antibacterial activity against three pathogenic bacteria: E. coli, S. aureus and V. harveyi. Significant activity was however noted with V. harveyi with values of inhibition zone 12 mm (methanol extract of wet animal), 13 mm (ethyl acetate extract of dry animal), and 18 mm (ethyl acetate extract of wet animal) (Duddu et al., 2017).

Cellana toreuma (Reeve, 1854)

Order: Patellogastropoda

Family: Nacellidae

Common name: Common intertidal limpet Distribution: South Korea, Mainland China, Taiwan, Japan, Ryukyu and Vietnam; Indo-West Pacific Ecology: These smooth, flat-pitched, benthic animals are found clustering in great numbers over the tops and sides of large rocks in lower tidal areas. Description: Shell of this species is oval in shape with flatter apex. A pale-colored muscle scar is seen. Its length varies from 20 to 30 mm. Biology Food and feeding: As for C. grata. Compound(s) and Activities Odd-chain fatty acids: From the ovaries of this species, oddchain fatty acids such as 7,18-nonadecadienoic (19:2Δ7,18), 11,18-nonadecadienoic (19:2Δ11,18), 7,20-heneicosadienoic (21:2Δ7,20), 11,20-heneicosadienoic (21:2Δ11,20), 14-pentadecenoic (15:1Δ14), 16-heptadecenoic (17:1Δ16), and 9,18-nonadecadienoic (19:2Δ9,18) have been isolated. Though all these compounds are of great use for human health, detailed research is needed on these compounds (Blunt et al., 2016).

Patella rustica (Linnaeus, 1758)

Order: Patelloogastropoda Family: Patellidae Common name: Rustic limpet, Lusitanian limpet Distribution: Northeast Atlantic; from the Mediterranean to the Atlantic coasts of the Iberian peninsula and northern Africa, including the Macaronesian Islands Ecology: It inhabits rocky shores of the intertidal fringe, usually at a depth of less than 3 m. Description: It attains a length of 17 mm. No other information is available. Biology Food and feeding: It forages on a low-lying epilithic and endolithic cyanophyceae (blue-green algae). Reproduction: Sea surface temperature might be a major determinant of the reproductive success of this species. In the Mediterranean south west, this species showed a sex ratio with a clear dominance of males compared to females. The

46

GSI of this species showed only one reproductive cycle per year, with a spawning peak coinciding with the cold period of the year. Maturation of gonads began in November, and a spawning peak was found in December. The sexual rest period runs from January to April, followed by oogenesis starting in May. Its spawning results in the shedding of eggs and sperm directly into the sea. After a period in the plankton, the short-lived free-swimming larvae (planktotrophic veliger larvae) settle at low levels on the shore or in damp crevices. As they grow, they slowly move upshore and inhabit different levels on the shore. Compound(s) and Activities Antimicrobial and antioxidant activities: The crude peptide extracted from this species showed antimicrobial and antioxidant activities. When the extracts were tested against eight strains of bacteria (E. coli, S. aureus, B. subtilis, S. typhi, E. faecalis, K. pneumoniae, S. pneumoniae, and P. aeruginosa) and one strain of fungi (C. albicans), there was a markedly higher antifungal activity, but little antibacterial effect was noticed. The minimum inhibitory concentration (MIC) of the extracts of this species was 13 mg/mL against all the strains of microorganisms tested except for E. faecalis (17 mg/mL), K. pneumoniae (17 mg/mL), and C. albicans (13 mg/mL). The antioxidant activity of the extracts of this species using the DPPH assay showed that scavenging ability on the DPPH radical was 79.77% at 0.39 mg/mL (Borquaye et al., 2015). Anti-inflammatory activity: The ethyl acetate fraction of this species showed moderate anti-inflammatory activity in the carrageenan-induced paw edema model in 7-day-old chicks (Borquaye et al., 2017).

Biology and Ecology of Pharmaceutical Marine Mollusks

a central or slightly anterior apex. Shell has clear growth rings as well as radiating ridges. The pallial tentacles that encircle the edge of the shell are transparent. Shells are grayish white with red or yellow markings. Biology Food and feeding: It feeds on a wide range of micro-organisms and algae, including Fucus spp. Reproduction: This species exhibited highly synchronized reproductive cycles, with well-defined breeding and resting periods. Gonad development started in September, and spawning took place from November–December to March on the northern and central Portuguese coasts (Ribeiro et al., 2009). Compound(s) and Activities β-Glucuronidase activity: The enzyme β-Glucuronidase (which catalyzes the breakdown of complex carbohydrates) produced by this species is reported to be more effective in hydrolyzing opioid-glucuronides. Further, this enzyme is used as a reporter gene to monitor gene expression (Anon., http:​ //www​.sigm​aaldr​ich.c​om/ca​talog​/prod​uct/s​igma/​g2174​?lang​ =en&r​egion​=IN).​

Fissurella cumingi (Reeve, 1849)

Patella vulgata (Linné, 1758)

Order: Patellogastropoda Family: Patellidae Common name: Common limpet, common European limpet Distribution: Western Europe Ecology: It inhabits rocky intertidal zones, usually with little seaweed cover, from the high shore barnacle zone to the edge of the sublittoral. It is found in every type of habitat, from rough, wave-exposed shores to calm estuaries. Description: P. vulgata is the largest limpet, growing up to 7 cm in diameter and 3 cm in height. It has a conical shell with

Order: Lepetellida Family: Fissurellidae Common name: Keyhole limpet Distribution: Southeast Pacific: Peru and Chile Ecology: This benthic species occupies the lowermost intertidal zone and immediate subtidal zone to 15 m on upper surfaces of rocks; deep tide pools at low tide; also on matrices of the tunicate Pyura praeputialis; depth range 0–15 m. Description: The size of an adult shell varies between 80 mm and 100 mm. No other information is available. Compound(s) and Activities Treating neoplastic diseases: The purified hemocyanins isolated from this species offer good scope for the treatment of neoplastic diseases (Anon., https​://ww​w.goo​gle.c​om/pa​tents​/ US84​36141​).

47

Marine Mollusks

Fissurella latimarginata (Sowerby I, 1835)

Ecology: It inhabits low intertidal and high subtidal levels; found under Lessonia sp. leaves on exposed rocky shores; encrusts on algae and on the undersides of large flat rocks at low tide; depth range 0–4 m. Biology: The size of an adult shell varies between 60 and 138 millimeters. No other information is available. Compound(s) and Activities Treating neoplastic diseases: The purified hemocyanins isolated from this species offer good scope for the treatment of neoplastic diseases (Anon. https​://ww​w.goo​gle.c​om/pa​tents​/ US84​36141​).

Order: Lepetellida Family: Fissurellidae Common name: Keyhole limpet Distribution: Southeast Pacific: from Chiclayo (Peru) to Rio Bio-bio (Chile) Ecology: It inhabits the rocky shores of intertidal and subtidal zones; associated with kelp beds; depth range 0–5 m. Biology: Size of an adult shell varies between 50 mm and 100 mm. No other information is available. Compound(s) and Activities Antitumor activity: A novel hemocyanin (FLH) isolated from this species has increased antitumor activity. This FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy (Arancibia et al., 2014). Anti-inflammatory activity: When C57BL/6 female mice were immunized with 200 µg of the hemocyanin of this species and then this FLH was coupled with 2, 4-dinitrofluorobenzene (DNFB) subcutaneously, high robust specific humoral immune response was observed in the hemocyanintreated mice (Ahmad et al., 2018). Others: The purified hemocyanins isolated from this species offer good scope for the treatment of neoplastic diseases (Anon., https​://ww​w.goo​gle.c​om/pa​tents​/ US84​36141​).

Fissurella maxima (Sowerby I, 1834)

Order: Lepetellida Family: Fissurellidae Common name: Giant keyhole limpet Distribution: Southeast Pacific: from Huarmey, Peru to Cape Horn, Chile

Megathura crenulata (Sowerby I, 1825)

Order: Lapetellida Family: Fissurellidae Common name: Giant keyhole limpet Distribution: Eastern Pacific: United States to Mexico Ecology: It is found on rocky substrate from intertidal to a depth of 33 meters; this animal is often found fastened onto rocks using suction. Description: This species is characterized by a slimy gray, black, or brownish skin covering its gray shell (that is, its shell is under its skin). Its mouth is present on the yellowish underside of its body. Top of the shell has a black central hole which is used to expel waste away from the gills and mouth to avoid the waste reentering its body. It can grow up to 25 cm in length. Their shells were used as currency and decoration by Native Americans. Biology Food and feeding: It has been reported to feed on filamentous cyanobacteria, diatoms, brown and red algae, marine seagrass, foraminifera, hydrozoans, bryozoans, nematodes, bivalves, gastropods, crustaceans, and tunicates. This omnivore feeds primarily on tunicates and red algae, which constitute more than 80% of its diet. Reproduction: This species is either gonochoric (sexes are separate) or successive hermaphrodite. Spawning occurs in late winter/springtime in most species. This species is believed to adopt dribble spawning (periodic pulsed spawning when environmental conditions are not ideal for mass spawning). It is a broadcast spawner. Embryos develop into

48

planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Anticancer activity: This species contains a hemocyanin (blood protein) called Keyhole limpet hemocyanin (KLH) which is a copper-containing respiratory protein, similar to hemoglobin in humans. It is an immunotherapeutic agent clinically. The major clinical use of KLH is specifically for the treatment of bladder carcinoma and other carcinomas, in particular epithelially derived adenocarcinomas. There are many other medical uses, such as stress assessment, understanding inflammatory conditions, diagnosis of Schistosomiasis, and treating drug addiction. It can also be used to fight autoimmune disorders, including Alzheimer’s disease (Kurokawa et al., 2002; McFadden et al., 2003; Harris and Markl, 1999).

Biology and Ecology of Pharmaceutical Marine Mollusks

Gram-negative (G-) Vibrio ichthyoenteri and fungi (yeast) Pityrosporum ovale at 250 microg/mL. Interestingly, abhisin treatment (50 microg/mL) decreased the viability of THP-1 leukemia cancer cells by approximately 25%. Further, abhisin has cytotoxicity against cancer cells but not normal cells (De Zoysa et al., 2009).

Haliotis discus hannai (Ino, 1953)

Haliotis discus discus (Reeve, 1846)

Order: Lepetellida Family: Haliotidae Common name: Disk abalone Distribution: Endemic to the waters off Japan and eastern Asia. Ecology: H. discus discus occurs predominantly shallower than 5 m water depth. Description: In terms of its characteristics, this species is closely allied to Haliotis kamtschatkana but is more elongated than the typical h. kamtschatkana. Interior shell surface has a peculiarly metallic luster, predominated by light bronze-green and coppery red. Size of the shell varies between 100 mm and 225 mm. Biology Food and feeding: This species feeds on particulate matter. Reproduction: The reproductive cycle in this species was divided into an inactive stage (January–February), early active stage (March–April), late active stage (May–July), ripe stage (August–October), and spent and degenerative stage (November–January). The main spawning period of this species was from August to October at Jeju Island (Kim et al., 2015). Compound(s) and Activities Antimicrobial activity: The antimicrobial peptide abhisin isolated from this species has been reported to inhibit the growth of Gram-positive (G+) Listeria monocytogenes,

Order: Lepetellida Family: Haliotidae Common name: Japanese abalone Distribution: From Siberia to China. Ecology: It lives in shallow subtidal habitats in depths of about 1–5 m. Description: It has a soft body surrounded by a mantle, an anterior head, and a large muscular foot. Shell is rounded or oval and it has a dome towards one end. Further, it is relatively thin and has a curved row of respiratory pores (rounded shell perforations overlying the respiratory cavity), three to five of which are open in this species. Interior surface of the shell has an iridescent appearance, being covered by a “nacre” or socalled “mother of pearl.” A sensory structure, the epipodium, is an extension of the foot that bears tentacles and projects beyond the shell edge in the living abalone. In this species, the epipodium has a brownish striped appearance. Size of the shell varies between 100 mm and 150 mm. Biology Food and feeding: As in H. discus discus. Reproduction: The reproductive cycle in this species was divided into an inactive stage (November–December), early active stage (January–March), late active stage (March– April), ripe stage (May–June), and spent and degenerative stage (July–October). The main spawning period of H. discus hannai was July to August at Jindo (Park et al., 2014). Compound(s) and Activities Anti-inflammatory activity: The mucosubstance by-products (AM) of this species were found to significantly lower nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-α, IL-1β, and IL-6 and enzymes iNOS and COX-2. The by-products of this species are therefore suggested to have notable

49

Marine Mollusks

anti-inflammatory potential, which promotes the possibility of their utilization as functional food ingredient (Rho et al., 2015). Ahmad et al. (2018) reported that the intestinal digest of this species has shown anti-inflammatory effects, suppressing the production of NO. Immune-modulatory activity: Two polysaccharides (AVPI, AVPII) (Aloe verapolysaccharides) extracted from the viscera of this species significantly stimulated lymphocyte proliferation, phagocytosis of macrophage, and natural killer-cell activity in a dose-dependent manner (Kim, 2013). Antioxidant and anticancer activities: H. discus hannai fermented using the fungus Cordyceps militaris mycelia (FHCM) showed antioxidant and anticancer activities. The antioxidant potential of FHCM was also determined on the basis of a ferric-reducing antioxidant power assay and 2,2’-​ azino​bis-(​3-eth​ybenz​othia​zolin​e-6-s​ulfon​ic acid) radical scavenging activity. Higher antioxidant and radical scavenging activities were observed in FHCM than in the unfermented C. militaris mycelia or H. discus hannai alone. FHCM also demonstrated an anticancer activity against the melanoma B16F10 cell line. In addition, FHCM cotreatment with doxorubicin showed an increased anticancer effect in both in vitro and in vivo. These findings suggest that the mycelial fermentation on H. discus hannai is highly suitable for pharmaceutical applications (Kim et al., 2016). Antioxidant activity: Two sulphated polysaccharide conjugates (termed ACP I and ACP II) isolated from this species have been reported to possess antioxidant activity (Zhu et al., 2008). Antitumor activity: An antineoplastic glycoprotein isolated from this species has shown strong tumor inhibition in ICR mice or albino, laboratory-bred strain of house (BALB/c) mice inoculated with allogeneic sarconema 180 or syngeneic Meth-A fibrosarcoma. An oligopeptide isolated from this species had a specific inhibitory effect on MMP-2/-9 and reduced the expression of proteins p50 and p65 in human fibrosarcoma (HT1080) cells in a dose-dependent manner (Ruiz-Torres et al., 2017). Anticoagulant activity: A novel glycosaminoglycan-like sulfated polysaccharide (AAP) (composed of galactosamine, glucuronic acid, fucose, and galactose) isolated from the pleopods of this species has shown anticoagulant activity. In-vitro anticoagulant assay indicated that AAP prolonged both the APTT and thrombin time (TT) with a 22.5 U/mg and 72.0 U/mg compared with standard heparin, respectively. The anticoagulant property of AAP was mainly attributed to powerful potentiation thrombin by anti-thrombin III (Li et al., 2011). Antihypertensive, antioxidant, and anticoagulant activities: The 80% ethanol extracts of the body and visceral portion of this species showed ACE activity and antioxidant and anticoagulant capacity. The ACE-inhibitory effect of the visceral portion was much higher than that of the body. Antioxidant capacity was increased with increasing concentration of 80% ethanol body extracts. The 80% ethanol visceral extracts showed a similar level of antioxidant capacity to the body extract in low concentration. There was no significant difference in the antioxidant activity between the body

and the visceral part. Anticoagulant capacity of 80% ethanol extracts was higher in the body part than the visceral part. APTT showed no significant difference between body and visceral part (Kim et al., 2006). Others: This species is a good source of taurine, which is isolated from its viscera. Taurine is a dietary supplement for epileptics, as well as for people who have uncontrollable facial twitches (Qian et al., 2014).

Haliotis diversicolor (Reeve, 1846)

Order: Lepetellida Family: Haliotidae Common name: Many-colored abalone, varicolored abalone Distribution: Northwestern Pacific Ocean: off Japan, Taiwan, Vietnam; off Australia (Northern Territory, Queensland, Western Australia); and in Indonesian waters (Bali) and off New Caledonia Ecology: It is a benthic species having a depth range 0–5 m. Description: Shell of this species is long and oval. Spire is very near the margin. Surface of the shell is spirally lirate; lines are unequal, rounded, and crossed by low folds. Its color pattern is reddish-brown, scarlet, and green in irregular patches and streaks. Coloration of shell is very variable, however. There are seven to nine oval perforations. Inner shell surface is silvery with light green and red reflections. Two sides of the shell are equally curved, and the back is quite convex. Columellar plate is rather narrow and flattened and slopes inward. Size of the shell varies between 25 mm and 85 mm. Biology Food and feeding: It feeds primarily on macroalgae. Reproduction: In Japan, the spawning season of Haliotis diversicolor has been reported to be between June and November. Studies made revealed that its spawning appears to be triggered only by typhoon-scale storms. Further, the timing of typhoons at the spawning ground may also be important for successful recruitment of this species. The hatch rate of eggs and subsequent larval development in this species are greatly influenced by changes in seawater temperature. The hatch rate of eggs was found to be about 95% at 27°C, but decreased to about 40% at 21°C (Onitsuka et al., 2007).

50

Compound(s) and Activities Anti-inflammatory activity: The organic extracts of this species showed anti-inflammatory activity (Ahmad et al., 2018) Antitumor activity: Its polysaccharides have shown antitumor activity in mice implanted with human nasopharyngeal cancer cells. These compounds have significantly inhibited the growth of implanted cells by inducing cell apoptosis and necrosis (Kim, 2013).

Haliotis laevigata (Donovan, 1808)

Biology and Ecology of Pharmaceutical Marine Mollusks

Compound(s) and Activities Antiviral activity: Crude hemolymph (20%, v/v) and lipophilic extract of the digestive gland of this species induced up to approximately 96% and 100% protection of Vero cells from HSV-1 infection, respectively. There was a reduction in the number of plaques (82%) and plaque size (32%) in all test samples (Dang et al., 2011). The in-vitro antiviral activity of this species was assessed against herpes simplex virus type 1 (HSV-1). The EC50 (effective concentration to inhibit HSV-1 plaque formation by ~50%) of the crude hemolymph (v/v) of this species was found to be 6.23% (Dang et al., 2011). Antimicrobial and immune-modulatory activities: The crude fresh abalone juice of this species showed antibacterial activity against S. aureus (Kim, 2013).

Haliotis rubra (Leach, 1814)

Order: Lepetellida Family: Haliotidae Common name: Smooth Australian abalone, greenlip abalone, whitened ear shell Distribution: Endemic to Australia and occurs off South Australia, Victoria, Western Australia and Tasmania Ecology: It lives in crevices and under boulders on rocky reefs in calm to rough water, at depths of up to 40 m. Description: This species features a distinctive green ring around the foot at the bottom of the shell. Its large, rather thin shell has an oval shape. Shell is nearly smooth but shows obsolete spiral lirae. Coloration is orange or orangescarlet, radiantly striped with continuous white flames. Coloration consists of continuous oblique stripes of scarlet and whitish color. There are 12 perforations, which are very small. Outline of the shell is oval, with the right and left margins about equally curved. Back of the shell is convex and rounded. Surface is sculptured with faint spiral threads and cords. Spire is moderately elevated. There are 2½ whorls. Inner surface is silvery. Nacre is almost smooth but shows traces of spiral sulci and is very minutely wrinkled. Columellar plate is rather wide, inward-sloping, flattened, and obliquely truncated at the base. Shell measures up to 18 cm. Biology Food and feeding: Its diet consists of a mix of macroalgae, particularly Ulva sp. Reproduction: It spawns between spring and late summer. It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults.

Order: Lepetellida Family: Haliotidae Common name: Blacklip abalone Distribution: Endemic to Australia; South Australia and Tasmania Ecology: It dwells in crevices, caves, and fissures and on vertical rock surfaces, from low tide to 40 m. Description: It has a large and much depressed shell which has a rounded-oval shape. It is sculptured with fine spiral cords. It shows radiating waves or folds above. There are six elevated and circular perforations. Shell outline is suborbicular and solid but not thick. Surface is either dark red, with a few radiating angular white patches; or dull red and green, streaked and mottled. Spiral cords of the outer surface are either nearly equal or have slightly larger ones at wide intervals. Whorls number a trifle over three. Inside shell is corrugated like the outer surface and is silvery and very brilliantly iridescent. Columellar plate is broad, flat, and obliquely truncated at its base. Cavity of the spire is wide and open, but shallow. Size of the shell varies between 3.5 and 20 cm. Maximum size is reached in less than 5 years. Biology Food and feeding: It feeds primarily on macroalgae. Reproduction: In Australia, abalone matures at about 9–10 cm shell length (3–6 years of age). Spawning occurs between

51

Marine Mollusks

spring and autumn with peaks in early spring and late summer (Anon., https​://ww​w.dpi​.nsw.​gov.a​u/__d​ata/a​ssets​/pdf_​ file/​0009/​37585​8/Bla​cklip​Abalo​ne.pd​f ). Compound(s) and Activities Antiviral activity: The lipophilic extract of the digestive gland of this species showed activity against HSVs; the hemolymph plasma acted against HSV-1a and HIV-1(Dang et al., 2015). Antithrombotic and anticoagulant properties: The prepared hydrolysates of the viscera (containing sulphated polysaccharides) of this species showed antithrombotic and anticoagulant properties. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through heparin cofactor II (HCII) I with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL. Fractionation concentrated HCIImediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anticoagulant activities by significantly delaying clotting time (Suleria et al., 2017).

Haliotis rufescens (Swainson, 1822)

Order: Lepetellida Family: Haliotidae Common name: Red abalone Distribution: From British Columbia, Canada, to Baja California, Mexico Ecology: This primarily subtidal species (also lower intertidal) lives in rocky areas with kelp and on the underside of overhanging ledges; depth range is from the intertidal zone to more than 180 m. Description: Shell of this species is large, thick, and domeshaped. It is usually a brick-red color externally. Typically the shell has three to four holes or respiratory pores, which are oval and slightly raised. These holes collectively make up what is known as the selenizone which form as the shell grows. Outside of shell is rough and lumpy or wavy. Inside of the shell is strongly iridescent and has a large central muscle. Shell length can reach a maximum of 31 cm, making it the largest species of abalone in the world. Biology Food and feeding: It is strictly vegetarian, feeding primarily on sessile macroalgae, kelp, and plankton. Reproduction: In this species, sexes are separate. Gonads of the females are green and those of the male are yellowish.

Spawning takes place from the middle of February through the first weeks of April. Males eject sperm and females eject eggs (over 2 million in one spawning season) through the water. In 10 days, the free-swimming larva, called veligers, settle to the bottom and, within 2 months, develop into small sized adults. By the age of 1 year, an abalone is about 1 inch long, and within 4 years it reaches sexual maturity, at about 12.5 cm in length (Anon., https​://an​imald​ivers​ity.o​rg/ac​count​ s/Hal​iotis​_rufe​scens​/). Compound(s) and Activities Antiviral activity: The unidentified bioactive macromolecules isolated from this species showed antiviral activity (Dang et al., 2011). The aqueous extract of this species displayed activity against polyomavirus, influenza A virus, and poliovirus (Dang et al., 2015).

Siphonaria diemensis (Quoy and Gaimard, 1833)

Order: Siphonariida Family: Siphonariidae Common name: False limpet Distribution: Southern Australia Ecology: It lives in reefs and on coastal shores; intertidally attached to rocks in sheltered to moderately exposed environments. Description: Shell of this species is conical, is wider than high, and has straight, white ridges that radiate from the center to the edge. Inside of shell is brown. Side of the foot (the fleshy bit) is almost black, which is unique to this species. Shell has a typical length of 30 mm. Biology Behavior: False limpets belong to the group known as pulmonates, meaning “lung breathing.” They trap air under their shell when water covers them during high tides so that they can still breathe. Food and feeding: It feeds primarily on encrusting brown algae (e.g. Ralfsia verrucosa and Scytosiphon lomentaria). Reproduction: The breeding season of this species collected from two zones at Griffith Point, San Remo, Victoria, was between August and May, and spawning was correlated with the phases of the moon. The reproduction rates were highly variable between seasons in Zone 1 and less variable

52

Biology and Ecology of Pharmaceutical Marine Mollusks

in Zone 2. It was suggested that the variation in reproductive rates between the different zones of this species was correlated with changes in food availability. Measurements of embryos and capsules at different developmental stages show that while the embryo increases in overall size from egg to hatching, the capsule size does not alter significantly during this period. The eggs hatched into a free-swimming veliger phase (Littlejohn, https​://re​searc​hdata​.ands​.org.​au/re​produ​ ctive​-patt​erns-​inter​tidal​-poin​t-vic​toria​/6799​44).

Van Wyk et al. (2008) reported on the occurrence of labdane diterpenes 6beta,7alpha-diacetoxylabda-8,13 E-dien-15-ol (1) and 2alpha,6beta,7alpha-triacetoxylabda-8,13 E-dien-15-ol (2) and three new metabolites, 6beta,7alpha,15-triacetoxylabda-8,13 E-diene (3); 3alph​a,11-​dihyd​roxy-​9,11-​seco-​chole​ st-4,​ 7-die​ n-6,9​ -dion​ e (4); and cholest-7-en-3,5,7-triol (5) in this species. Among these compounds, compounds 1, 2, and 4 exhibited moderate activity (3–25 microM) against the WHCO1 human esophageal cancer cell line.

Compound(s) and Activities Antibacterial activity: Among the antibiotic compounds diemensin A and diemensin B isolated from this species, diemensin A showed antibacterial activity by inhibiting the growth of S. aureus and B. subtilis at 1 µg/disc and 5 µg/disc, respectively. (Datta et al., 2015).

Trimusculus costatus (Krauss, 1848)

  6beta,7alpha-diacetoxylabda-8,13 E-die​n-15-​ol 

2a​lpha,​6beta​,7alp​ha-tr​iacet​oxyla​bda-8​,13 E-dien-15-ol Order: Ellobiida Family: Trimusculidae Common name: False limpet, button snail Distribution: Eastern Pacific Ecology: It lives in intertidal zones on rocky shores. Biology: This shelled pulmonate is a medium-sized airbreathing sea snail. Shells of this species are small, white, almost perfectly circular in outline, and only moderately elevated; thus, the shells are somewhat reminiscent of traditional white shirt buttons. It has a size of 15.5. mm.

6beta,7alpha,15-triacetoxylabda-8,13 E-diene

Biology Food and feeding: These animals lead a mostly sedentary life and feed by means of a mucous net that they secrete to filter food particles from the water column at high tide. Reproduction: Not reported. Compound(s) and Activities Anticancer activity: A novel secosterol isolated from this species showed anticancer activity against WHCO1 esophageal cancer cell line with a GI50 value of ∼3 μM (Ciavatta et al., 2017).

Secosterol

3alph​a,11-​dihyd​roxy-​9,11-​seco-​chole​st-4,​7-die​n-6,9​-dion​e

cholest-7-en-3,5,7-triol

53

Marine Mollusks

Trimusculus peruvianus (Sowerby I, 1835)

Order: Ellobiida Family: Trimusculidae Common name: Not designated Distribution: Peruvian coast Ecology: It lives in intertidal zones on rocky shores; found on rocks at low water. Description and Biology: Not reported.

Others: New labdane diterpenes 6β -hydroxy-labda-8, 13-dien-15-ol and 3, 19-isovaleroyl-6beta, 9alpha-dihydroxylabda-Delta(8,17), 13-dien-15-oic acid have been isolated from this species. Their pharmaceutical activities are, however, yet to be discovered (Diaz-Marrero et al., 2008).

6β-hydroxy-labda-8, 13-di​en-15​-ol

Compound(s) and Activities Anticancer activity: The compound C‐21 hydroxylated sterol isolated from this species showed anticancer activity against human HCT‐116 and HT29 colon cancer cell lines with GI50 values of ∼6 μM (Ciavatta et al., 2017).

3​,19-i​soval​eroyl​-6,9-​dihyd​roxyl​abda-​8,17,​13-di​en-15​-oic acid

Turritella acutangula (Linnaeus, 1758) (=Turritella duplicata) C‐21 hydroxylated sterol Two new sterols, 1 ((20R​)-cho​lest-​5,24-​diene​-3β,7​β,21-​triol​) and 2 ((20R​)-cho​lest-​7,24-​diene​-3α,5​α,6β,​21-te​trol)​ isolated from this species exhibited moderate in-vitro cytotoxic activity against human colon carcinoma cell lines (Díaz-Marrero et al., 2003).

(20R)​-chol​est-5​,24-d​iene-​3β,7β​,21-t​riol ​

​(20R)​-chol​est-7​,24-d​iene-​3α,5α​,6β,2​1-tet​rol

Order: Caenogastropoda Family: Turritellidae Common name: Duplicate turret, screw shell Distribution: Indo-West Pacific: from Madagascar to Indonesia; north to the Philippines and south to northern Queensland Ecology: This reef-associated, benthic species inhabits sandy, subtidal coastal waters. Description: Shell of this species is slender and more elongated. Its height is at least four times as much as the maximum width of the body whorl. Whorls are more conspicuously bulged in the middle, and the sutural constrictions consequently appear deeper. Surface is traversed by fine spiral striae as well as by strongly raised spiral ridges. Strongest rib occurs somewhere near the middle and is followed above by a series of ribs. Coloration of shell is browning but more often

54

tends to be more or less strongly tinged with blue. Maximum length of the shell is 18 cm. Biology Food and feeding: It is a suspension-feeding marine gastropod. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antioxidant activity: The organic extracts of this species showed antioxidant activity (Pachaiyappan et al., 2014).

Turritella attenuata (Reeve, 1849)

Order: Caenogastropoda Family: Turritellidae Common name: There are no common names. Distribution: India; Thailand Ecology: This reef-associated, benthic species inhabits sandy coastal waters. Description: Shell of this species largely resembles T. acutangula. Maximum shell length is 13.8 cm. Biology As in T. acutangula. Compound(s) and Activities Antioxidant activity: The organic extracts of this species showed antioxidant activity (Pachaiyappan et al., 2014). Anticoagulant activity: The organic extract of this species showed anticoagulant activity of 37 USP units/mg (Periyasamy et al., 2013).

Biology and Ecology of Pharmaceutical Marine Mollusks

Ecology: It is seen in rocky intertidal environments; in groups on large boulders and seawalls; active at low tide. Description: It has a conical shell, with strong squarish spiral cords. Color of the shell is blackish to cream, sometimes with white or yellowish spots. Shell opening is wide and inner surface is white, sometimes with dark purple grooves. Operculum is thin, hornlike, and dark colored. Body of the animal is pale with a small foot. There are long tentacles with dark bands. Size of the shell varies between 13 mm and 35 mm. Biology Food and feeding: It is a herbivore, grazing on microalgae covering rocky areas. Reproduction: It is a gonochoristic, ovoviviparous species that rears its embryos in large brood pouches. Embryos may hatch at the veliger stage to become planktotrophic larvae, hatch at a late veliger state as lecithotrophic larvae, or be brooded throughout the embryonic development stage to hatch as juvenile snails. Mating is observed in P. sulcatus to occur during summer, where copulation between male–female pairs is frequently observed (Anon., https​://ww​w.gbr​i.org​.au/S​pecie​ s/Pla​naxis​sulca​tus.a​spx?P​ageCo​ntent​ID=22​25). Parasite: P. sulcatus often plays host to a large diversity of trematode species (Anon., https​://ww​w.gbr​i.org​.au/S​pecie​ s/Pla​naxis​sulca​tus.a​spx?P​ageCo​ntent​ID=22​25). Compound(s) and Activities Anticancer activity: The bioactive cembranoid compounds dihydrosinularin and 11-epi-sinulariolide isolated from this species showed marginal antineoplastic activity against P-388 lymphocytic leukemia (Sanduja et al., 1986).

Planaxis sulcatus (Born, 1791)

  Dihydrosinularin 11-epi-sinulariolide Cytotoxic activity: The bioactive compound planaxool (a novel Cembranoid) isolated from this species has shown significant cytotoxic activity (Alam et al., 1993).

Order: Caenogastropoda Family: Planaxidae Common name: Tropical periwinkle, furrowed clusterwink, sulcate planaxis Distribution: Indo-Pacific: Red Sea; off Mozambique, Kenya, Madagascar, Tanzania and off Mauritius; Chagos, Aldabra and the Mascarene Basin

Planaxool

55

Marine Mollusks

Euthria cornea (Linnaeus, 1758) (=Buccinulum corneum)

Antiviral activity: The organic extract of this species exhibited antiviral activity against human T-cell leukemia virus type 1 by inhibiting viral transcription and DNA/RNA synthesis (i.e., by inhibition of virus DNA polymerase α and reverse) (Dang et al., 2015; Silvestri et al., 1995).

Cerithidea cingulata (Gmelin, 1791)

Order: Caenogastropoda Family: Buccinidae Common name: Spindle euthria Distribution: Atlantic Ocean: Portugal and Morocco; Mediterranean Sea Ecology: It is found at depths of 5–30 m, mainly on rocky substrates. Description: This mollusk has a robust fusiform shell with a sharp apex. Opening is oval and wide, with slight striae. Horny operculum is oval. Coloration of the shell is quite variable, with irregular dark spots on a brownish-gray background. Shell size of E. cornea varies between 20 mm and 80 mm. Biology Food and feeding: It is a carnivorous species that preferentially feeds on small bivalves. It uses its sturdy foot to slightly open the prey valves and suck the tissues with the long mouth. Reproduction: Females of this species often gather at the time of laying. They lay eggs that are enclosed in yellowishwhite chitinous capsules. There are several hundred eggs per capsule, and each spawn contains many capsules, from several individuals, stacked on top of each other to form a cluster. Compound(s) and Activities Antimicrobial activity: The esters of p-hydroxybenzoic acid viz. (Kelletinin I and Kelletin A) extracted from this species showed antimicrobial activity by inhibiting bacterial DNA and RNA synthesis (Orlando et al., 1991).

  Kelletinin I

Kelletinin A

Order: Caenogastropoda Family: Potamididae Common name: Girdled horn shell Distribution: Indo-West Pacific: from India and Sri Lanka to Papua New Guinea; north to Japan and south to central Queensland. Ecology: This benthic species occurs in shallow sheltered places and monsoon drains near the sea; also on brackish or supersalted fishponds and mangrove mudflats; usually living in the upper bottom layer of mud, which is almost liquid. Description: Shell of this species is conical with spirals of large beads. Shell opening is large and flared with a spoutlike tip. Operculum is thin and dark with tight spirals. Its maximum length is 4.5 cm. This species is extensively collected for food and the shell is used to make lime in the Philippines. Biology Food and feeding: It grazes on tiny particles growing or settling on the muddy bottom, such as diatoms, bacteria, and detritus. Reproduction: In the Philippines, mature snails occurred throughout the whole year in brackish water ponds. Fecundity (=number of oocytes) increased with size in mature females; an average 25-mm female produced about 1,500 oocytes, and larger females produced a maximum of about 2,500 oocytes. Egg strings laid on the pond bottom were 45–75 mm long; an average 64-mm string contained 2,000 eggs. The density of egg strings was highest during March–September. Eggs hatched after 6–7 days into planktonic veligers, which in turn settle on the pond bottom 11–12 days later as juveniles 2–6 mm long (Lantin-Olaguer and Bagarinao, 2001). Compound(s) and Activities Antibacterial activity: The ethyl acetate crude extract of this species exhibited the highest activity against S. aureus (4.5 mm), followed by B. cereus and Enterobacter aerogenes,

56

Biology and Ecology of Pharmaceutical Marine Mollusks

with inhibitory zones of 3.5 mm each. The acetone extract was found to inhibit V. cholerae with a zone of inhibition of 3.5 mm, followed by E. aerogenes with an inhibition zone of 2 mm. The ethyl acetate extracts were able to inhibit V. cholerae with a zone of inhibition of 3 mm and the diethyl ether extracts against B. cereus (2 mm), E. aerogenes, and K. pneumoniae (Kumar, 2011).

concentrations of 10, 20, 30, 40, and 50 mg/mL were 12.19%, 33.97%, 43.25%, 54.48%, and 57.91%, respectively (Cahyani et al., 2015). Antioxidant activity: The methanol extract of this species showed potent antioxidant activity with an IC50 value of 58.2 ppm with a comparison vitamin C of 3.6 ppm (Purwaningsih, 2012).

Cerithidea obtusa (Lamarck, 1822)

Telescopium telescopium (Linnaeus, 1758)

Order: Coenogastropoda Family: Potamididae Common name: Obtuse horn shell, mud creeper, red chut-chut snail, red snail conch Distribution: Indo-West Pacific: from Madagascar and India to eastern Indonesia; north to the Philippines and south to Australia Ecology: It dwells in muddy coastal areas; animals often concentrate in the wettest spots, when the mud bottom is partly dry at low tide; occurs at the low tide mark. Description: Shell of this species is squat (not so elongated) with ribs of fine beads. Shell opening is wide and has a thick flaring lip. Tip of the shell is usually broken. Operculum is round and dark. In addition to a pair of eyes on tentacles, it has a third eye, called the pallial eye, on its mantle margin. Living snail does indeed have red eyes as well as a reddish margin around the foot. It grows to a maximum length of 6 cm. It is used as a food in Southeast Asia.

Order: Coenogastropoda Family: Potamididae Common name: Horn snail, telescope snail, mud whelk, mangrove whelk Distribution: Indo-West Pacific: Australia, Madagascar, Pakistan, Philippines, Sri Lanka, West Bengal (India). Ecology: It is a benthic, marine, brackish water, and freshwater species; found in mud flats, alkaline lakes, small ditches, shallow pools, or canals or among the pneumatophores of mangroves; active during ebb-tide; often partly buried in mud, with only top of spire projecting. Description: This large snail has an 8–15 cm-tall conical shell which is beautifully marked. Whorls are spirally grooved, flat, and heavy. Flat base is separated from the columella by a deep channel. Edge of the aperture descends in a sweeping curve, forming a corkscrew appearance. Labial lip is curved. Outer lip is thin, not flared, and smooth except for weak serrations anteriorly. Operculum is round and relatively small. Shell color is uniformly dark brown. This species has two types of shell forms. One, which is of the typical form, shows a regular conical shape with strong spiral grooves; the other is smooth, suddenly broadening at the body whorl, with much stronger columellar folds. “Smooth type” has greater weight owing to its external lip or due to the coating of the shell. Shell reaches a maximum length of 15 cm. Animal of this species is velvety black with a highly extendible proboscis. There is a third eye on its mantle margin, in addition to a pair of eyes at the tentacles. It can stay out of water for long periods of time.

Biology Food and feeding: As in C. cingulata. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antidiabetic activity: The organic extracts of this species containing alkaloids, flavonoids, and triterpenoids have shown antidiabetic activity. While the methanol extract had the highest percentage of α-glucosidase inhibition at 40.10%, the hexane and ethyl acetate extracts had a very low percentage of α-glucosidase inhibition at 2.01% and 0.64%, respectively. The values of α-glucosidase inhibition in the extract

Biology Food and feeding: It moves on mud floors, slowly extending its proboscis, which grazes the muddy substratum that is mixed with microalgae. After grazing, it crawls with the help of its foot.

57

Marine Mollusks

Reproduction: Sexual activities of T. telescopium happen at all times during the active period. Sexes are separate, and there is no external sexual dimorphism. Observations indicated that the activity begins when the male, by means of its foot, holds the female’s shell. It maneuvers the female so as to position the female’s aperture opposite the male aperture. When this position is reached, the male will penetrate its head and foot into the opening of the female’s aperture. It is a broadcast spawner. Embryos develop into planktonic trochophore larvae and later into juvenile veligers before becoming fully grown adults.

Compound(s) and Activities Antimicrobial activity: The peptide obtained from this species potently inhibited the growth of E. coli (Ghosh and Playford, 2003). Similarly, ammonium sulfate precipitated protein (SF-50) isolated from the sperm theca gland of this species showed activity against E. coli (Pakrashi et al., 2001; Kiran et al., 2014. Antiangiogenic activity: The methanolic extracts (200 µg) of this species showed a fairly higher degree of antiangiogenic activity with an inhibitory percentage (64.63%) of the VEGF-induced neovascularization. Further, in the experiment relating to in-vivo antiangiogenic activity, these extracts exhibited the most noticeable inhibition (42.58%) of the corneal neovascularization in rats (Gupta et al., 2014). The significant antiangiogenic activity evinced by the extract of this species merits further investigation for ocular neovascular diseases. Hypotensive effect: Intravenous administration of the tissue extract of this species produced a decrease in blood pressure (hypotensive effect) in anesthetized rats. The above extract has also been reported to produce potent esterase, cholinesterase, phospholipase, phosphatase, and protease activities (Samanta et al., 2008). Antioxidant activity: The crude methanolic extracts of this species have been reported to show DPPH radical scavenging activity (Pachaiyappan et al., 2014). Others: The cytosol fraction of spermatheca and/or the ovotestis gland of this species was found to have antimicrobial, antiprotozoal, antifertility, and immunomodulation properties. Further, its organic extract was able to restrict the induced tumor (sarcoma-180) growth in mice concomitantly with an increased life span of the tumor-bearing mice, but without any hematopoietic toxicity. This antitumor property was thought to be mediated immunologically as it was also found in other aspects of pharmacological actions of this extract; hence, it could be developed as a potent immunomodulator to be used for various pathological conditions in general, but in cancer in particular (Roy et al., 2010).

Scaphander lignarius (Linnaeus, 1767)

Order: Cephalaspidea Family: Scaphandridae Common name: Woody canoe-bubble Distribution: European waters and in Mediterranean Sea; North Sea Ecology: It occurs in muddy sand; depth range sublittoral–700 m. Description: Shell of this species is solid, glossy, and opaque; and it has a sculpture of spiral lines crossed by longitudinal lines, with pigment distributed along some of the lines. Color of the shell is green, yellow, or brown. Shell attains a maximum length of 6 cm. Body (animal) is white or orange. Head is very short, squat, and indented anteriorly; and tentacular processes are smooth, short, and conical. Parapodial lobes extend from anterior end of head shield to about middle of shell, and pallial lobe is also visible. It is a burrower, preying on infaunal worms and lamellibranches. Biology Food and feeding: This species feeds on foraminiferans, bivalves, gastropods, scaphopods, and occasionally sipunculids. Reproduction: It is sexual and individuals are hermaphrodite. As with all gastropods, there is a larval stage, viz. trochophore. Compound(s) and Activities Cytotoxic activity: This species contained unusual PUFAs such as several ω3 fatty acids and the ω7 heneicosa-5,8,11,14tetraenoic acid (21:4 n-7), which were found to be active against a range of human cancer cell lines (melanoma, colon carcinoma, and breast carcinoma). The ω7 PUFA was significantly more cytotoxic in comparison with reference ω6 arachidonic acid (ARA) and ω3 EPA. A noteworthy nonselective cytotoxicity against normal lung fibroblasts was also established (Vasskog et al., 2012). The PUFAs, viz. EPA and ARA, showed cytotoxic activity against normal human fibroblasts (CCD-41-SK) at ~60 µg/mL and ~30 µg/mL, respectively. Those concentrations were some two to three times higher than the concentration needed to kill

58

Biology and Ecology of Pharmaceutical Marine Mollusks

100% of human breast tumor cells (ZR-75-1). Three representative PUFAs, viz. ARA (20:4 n-6), EPA (20:5 n-3), and heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) (HTA) were chosen for further cytotoxicity studies against a set of cancer and normal cell lines. All the compounds were able to kill cancer cells in a dose-dependent manner as shown below. Cytotoxicity of ARA, EPA, and HTA against Selected Cell Lines 50% Cytotoxicity (µg/mL) Cell line

EPA

ARA

HTA

Normal lung fibroblast (MRC5) Colon carcinoma (HT29) Melanoma (A2058)

90 93 45

90 76 43

42 41 31

Breast carcinoma (MCF7)

66

68

44

Source:  Vasskog et al. (2012).

EPA

Distribution: Indo-West Pacific; Northern Marianas, Hawaii, and Easter Island Ecology: It lives in high intertidal areas in rocky habitats of the splash zone; found at highly protected to exposed sites, viz. overhanging tree limbs. Description: Smaragdinella calyculata is green, sometimes with brown or white blotches along the edge of the parapodia. It has a caplike shell partially enveloped by mantle, and shell is flattened with a greatly expanded aperture and low spire. Shell attains a maximum length of 13 mm. Animal attains a size of 2.5 cm. Biology Food and feeding: It is nocturnally active, feeding on microalgae growing on rocks or tree limbs while the tide is low. Reproduction: It is a simultaneous hermaphrodite. It lays a flaplike, pale-yellow egg mass that is attached by one edge. Compound(s) and Activities Cytotoxicity: The polypropionate compound nalodional isolated from this species showed significant cytotoxicity against P388 mouse leukemia cells with an LD50 (Lethal dose 50%) value of 3.5 µg/mL) (Tringali, 2003).

ARA

HTA Others: The conjugated polyketides, viz. Lignarenones A and B, isolated from this species have served as alarm pheromones. The pharmaceutical uses of these compounds are, however, yet to be discovered (Vasskog et al., 2012).

Nalodional

Bulla striata (Bruguiere, 1792)

 

Lignarenone A        Lignarenone B

Smaragdinella calyculata (Broderip and Sowerby, 1829)

Order: Cephalaspidea Family: Smaragdinellidae Common name: Calyx bubble

Order: Cephalaspidea Family: Bullidae Common name: Common Atlantic bubble, striate bubble Distribution: Throughout the tropics and subtropics on both sides of the Atlantic, including the Mediterranean, Morocco, Canaries, the Azores, and Florida Ecology: It inhabits soft sediment habitats of shallow waters. Description: Shell of this species is thin and usually delicate, smooth, oval, and inflated with an umbilicate (depressed) spire. Aperture is longer than the shell and is rounded at both ends, narrow posteriorly and wide anteriorly. Lip is thin and slightly

59

Marine Mollusks

constricted centrally. There is no operculum. Foot is well developed and foot and mantle are slightly translucent. There are no parapodia (fleshy winglike outgrowths). Head is broadened and lacks tentacles. Small eyes occur on the dorsal surface of the cephalic shield. Color of the shell is variable, from pale reddish gray to brown-gray, mottled with darker smudged purplish brown dots. Aperture is white. Maximum shell length is 35 mm. Biology Association: The empty shells of dead B. striata are often an important resource for hermit crabs. Food and feeding: It is omnivorous. This species consumes not only epiphytes and diatoms but also seagrass (Zostera noltii) itself, which is an uncommon feature among mollusks. Reproduction: In this species, reproduction involves copulation with internal fertilization between hermaphroditic individuals. Fertilized eggs are deposited as an external egg mass, which individuals may attach to seagrass blades. The egg masses are long, irregularly coiled, gelatinous cylindrical cords. Larval development is planktotrophic. Veligers hatch 4–5 days after egg deposition. Compound(s) and Activities Compounds: Polypropionate secondary metabolites such as aglajne 1, aglajne 2, and aglajne 3 have been isolated from this species. Initial research has shown that aglajne 3 is very toxic against the mosquito fish Gambusia affinis and the brine shrimp Artemia salina. Further intensive research, is needed, however, to identify the therapeutic functions of these compounds (Tringali, 2003).

Distribution: Eastern Pacific Ocean: West coast of North America from Alaska to Baja California and Ecuador Ecology: It occurs in shallow, protected waters on mud or sandy bottoms; and in estuaries and sheltered bays down to depths of 10 m. Description: B. gouldiana has a semitransparent, paper-thin, globose shell that is brown or pale violet. Head, mantle, and foot are yellowish-brown with mottled whitish dots. Aperture is wide anteriorly and narrow posteriorly. Its semitransparent mantle is brown with varying degrees of mottled bluish pigmentation. Shell of this species reaches over 55 mm in length. Biology Behavior: B. gouldiana is most active at night, spending the day buried in the sand or mud. Food and feeding: It is a herbivore, feeding on green algae. Reproduction: Egg mass is a yellow-to-orange tangled string of jelly, containing oval capsules. Each one contains up to 25 eggs, which develop into veliger larvae. Compound(s) and Activities Compounds: The polypropionate compounds niuhinone-B, 5,6-dehydroaglane-3, and isopulo’unone have been isolated from this species. Though these compounds play a key role in the elucidation of cellular processes and biological mechanisms, further research is needed on their therapeutic functions (Spinella et al., 1993).

 

 

Niuhinone-B      5,6-dehydroaglane-3

Aglajne 1            Aglajne 2

Aglajne 3

Isopulo’unone

Bulla gouldiana (Pilsbry, 1895)

Bullacta exarata (Philippi, 1849)

Order: Cephalaspidea Family: Bullidae Common name: California bubble, Gould’s bubble, or cloudy bubble snail

Order: Cephalaspidea Family: Haminoeidae Common name: Korean mud snail Distribution: Western Pacific: China, Korea, and Japan

60

Ecology: This demersal species occurs in intertidal flats, including the supratidal zone and subtidal zone. Description: Shell of this species is bullate, fairly thick, white, and spirally striate, with a well-developed periostracum. There is no spire and no umbilicus. Columella is smooth and simple. Aperture extends for the whole length of the shell and is narrower above than below. Apertural lip extends upwards beyond the apex of the shell. Height of the shell is 8 mm and width 6 mm. It is an important food item in eastern China.

Biology and Ecology of Pharmaceutical Marine Mollusks

activity against E. coli, S. aureus, and B. subtilis. BEP-1 also showed activity against human pathogen strains (S. epidermidis, E. coli, and Methicillin-resistant S. aureus) (Jian-yin et al., 2011).

Navanax inermis (Cooper, 1863)

Biology Food and feeding: It is a herbivore, feeding primarily on diatoms. Reproduction: B. exarata is a hermaphrodite. Compound(s) and Activities Antioxidant activity: The mannoglucan BEPS-IB isolated from this species exhibited positive antioxidant activity in scavenging superoxide radicals and reducing power (Liu et al., 2013). Antioxidant and antitumor activities: The three polysaccharides (BEP1, BEP2, and BEP3) isolated from this species were found to possess antioxidant activities in a dose-dependent manner. The BEP3 exhibited stronger antioxidant activities than BEP1 and BEP2. Furthermore, BEP3 showed significant inhibitory effects on growth of Bcap37 breast cancer cells, SW1990 pancreatic cancer cells, and HeLa cervical cancer cells, and the IC50 were 135.3, 147.5, and 172.6 μg/mL, respectively. The highest inhibition rates of BEP1 and BEP2 were approximately 10% against three cancer cells. The data obtained from in-vitro models indicates that polysaccharides of this species could be explored as novel and potential natural antioxidants and cancer-prevention agents for use in functional foods (Zhang et al., 2012). Anticancer activity: The peptides isolated from these species, namely BEPT II and BEPT II-1, significantly inhibited the proliferation of PC-3 cells in a time- and dose-dependent manner. BEPT II-1 for 24 h increased the percentage of the early stage of apoptotic cells from 11.22% to 22.09%. These data support the theory that BEPT II-1 has anticancer properties and merits further investigation to understand the mechanisms of BEPT II-1-induced apoptosis in PC-3 cells (Ma et al., 2013). Liao et al. (2017)​reported that a novel polysaccharide conjugate (protein complex BEPS-IA) of this species induced G1-phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Antitumor activity: The sulphated polysaccharide coded as BEMPA exhibited highest inhibitory effects on growth of B-16 melanoma cells, and its IC50 was 31.1 lg (Zhang et al., 2012). Lin et al. (2012) reported that the peptide compound isolated from this species could inhibit the PC-3 cells’ growth and could have antitumor activities on prostate cancer. Antibacterial activity: Three isolated peptides of this species (coded as BEP-1, BEP-2 and BEP-3) were found to show

Order: Cephalaspidea Family: Aglajidae Common name: California aglaja Distribution: Eastern Pacific: From Monterey Bay, California to Laguna Manuela, Mexico; Gulf of Mexico Ecology: It is found on sandy, muddy, and rocky bottoms in bays and on open coast; depth range 5–8 m. Description: N. inermis, probably the largest aglajid, is dark brown to black with a pattern of cream to yellow longitudinal lines, sometimes broken and sometimes replaced by a close pattern of spots. Parapodia have an orange line along the edge and an inner line of bright blue spots or dashes. Pallial lobes at the back of the posterior shield are relatively large and taper to a point. This species can reach a total length of more than 22 cm. Biology Food and feeding: Navanax inermis feeds on other sea slugs, such as bubble shells and sometimes nudibranchs. On sheltered muddy or sandy bottoms, it feeds on bubble shells such as Haminoea virescens and B. gouldiana. Reproduction: N. inermis is an internally fertilizing, simultaneous hermaphrodite. N. inermis is a simultaneous hermaphrodite. Copulation can occur in groups, commonly referred to as chains, of up to four individuals. In the southern portion of its range, this species spawns year round, producing upwards of 800,000 eggs at a time. After 7 to 19 days of development, embryos are released and live as plankton (Leonaki and Lukowiak, 1985). Compound(s) and Activities Compounds: The compounds navenone A, B, C, and isopulo’upone have been isolated from this species. Though the first three compounds serve as pheromones, no other pharmaceutical properties of any of these compounds are yet known (Tringali, 2003; Alam and Thomson, 1997).

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Marine Mollusks

 

Navenone A         Navenone B

Navenone C

Isopulo’upone

Nembrotha sp. Compound(s) and Activities Antimicrobial activity: A potent antimicrobial agent, viz. tambjamine, has been isolated from the crude extract of this species. This compound was found to be active against B. subtilis at 5 µg/disc (Fisch et al., 2017).

Ecology: It is a benthic species living on a mixture of coral and basaltic sand bottom at about 10 m depth. Description: It is a sea slug of relatively cylindrical shape, being quite large, reaching a maximum length of 10 cm. At the front of the body, a large cephalic shield protects the head. On the flanks, parapodia start from the foot. On the back of the body, a posterior shield hides the invisible flat shell and ends with two small lobes that are sometimes seen raised. Foot forms two lobes, which are rather flaccid. This species is very variable in color. Body of this species can be very dark, almost black in color, and varies in color from dark brown to medium brown, and brown and white speckled. Biology Food and feeding: These slugs are active crawlers and can feed upon larger prey (e.g. fish, bulloid gastropods, polychaetes, flatworms, crustaceans, ctenophores, and other sea slugs). Reproduction: P. depicta is, like all cephalaspids, a synchronous hermaphroditic species; that is, it has both sexes, male and female, and both are functional at the same time. At the end of the mating, the partners will separate and each of those who received the sperm will be able to go and lay. The laying is a filament of cylindrical, clear eggs. It is usually covered with sand or even buried. From these fertilized eggs, the planktonic veliger larvae appear after a few days. Then the survivors will land on a suitable substrate and begin their metamorphosis to the adult form (Anon., http:​//dor​is.ff​essm.​ fr/Es​peces​/ Phil​inops​is-de​picta​-Agla​ja-ch​arnue​-1117​). Compound(s) and Activities Antibiotic: The compound aglajne 1, an acyclic polypropionate isolated from this species, may serve as an antibiotic, and further research is needed on this compound (Cimino et al., 1985).

Tambjamine

Philinopsis depicta (Renier, 1807) (=Aglaja depicta)

Order: Cephalaspidea Family: Aglajidae Common name: Not reported Distribution: Northeast Atlantic and the Mediterranean: Europe

Aglajane 1 Cardiovascular effects: The compound adenosine isolated from this species showed cardiovascular effects, viz. slowing down of the heart and hypotension in mice and guinea pigs (Cimino et al., 1986).

Adenosine

62

Philinopsis speciosa (Pease, 1860)

Biology and Ecology of Pharmaceutical Marine Mollusks

cancer. In yet another study, the GI50 values for kulokekahilide‐2 were ∼19 and ∼4 nM in murine P388 leukemia and human HeLa cervix carcinoma cells, respectively (Ciavatta et al., 2017).

Order: Cephalaspidea Family: Aglajidae Common name: Showy headshield slug Distribution: Indo-Pacific; Eastern Pacific Ecology: It lives on open sand and Halimeda kanaloana beds at depths of 9–27 m. Description: Ground color of the animal ranges from a light translucent brown to an opaque dark brown or even black. There are a pair of yellow to orange-brown parallel lines on the headshield on either side of the midline. Its white spots range from quite small to very large, the large white markings being somewhat broken by brown speckling. Margin of the parapodia is colored with black, blue, and orange-yellow markings, which can sometimes form lines. Foot appears to be of similar color to the dorsal surface. Color of the animal is extremely variable. It attains a maximum size of 7.6 cm. Biology Food and feeding: Mature animals are usually nocturnal. They feed on sand-dwelling haminoeids. This species has also been observed eating the sea hare, Stylocheilus striatus. Reproduction: Its egg mass is an elongate, white sack composed of a tangled egg string. Egg masses are typically anchored in sand and are often found in pairs, suggesting that both animals in a mating pair may lay before separating. Compound(s) and Activities Cytotoxic activity: Cytotoxic depsipeptides kulokekahilides 1, 2 have been isolated from this species. Kulokekahilide‐1 displayed growth inhibitory effects with the GI50 of ∼2 μM in murine P388 leukemia cells, while kulokekahilide‐2 displayed higher potency in this cell line with a GI50value of ∼4 nM. In addition, kulokekahilide‐2 displayed GI50 values of ∼8 and ∼15 nM in the human SK‐OV‐3 ovarian and the MDA‐MB‐435 breast cancer cell lines, respectively. The mean GI50 value calculated for the three P388, SK‐OV‐3, and MDA‐MB‐435 cancer cell lines is thus ∼9 nM. Because the GI50 value of kulokekahilide‐2 in A‐10 (nontransformed rat [Rattus norvegicus] aortic cells) cell line is ∼60 nM,378, it behaves as a bioselective compound, at least within the few cell lines in which it has been assayed. In another study, the mean GI50 value of kulokekahilide‐2 was ∼0.2 nM in three other cancer cell lines, namely human A549 NSCLC, K562 chronic myelogenous leukemia, and MCF‐7 breast

Kulokekahilide 1

 

Kulokekahilide-2

The cyclodepsipeptide kulolide 1 isolated from this species displayed growth inhibitory activity in micromolar range against murine L‐1210 (GI50 = ∼1 μM) and P388 (GI50 = ∼3 μM) leukemia cells (Ciavatta et al., 2017).

Kulolide 1 The compounds viz. kulolide 2, kulolide 3, and kulokainalide-1 isolated from this species also showed moderate cytotoxicity (Ciavatta et al., 2017; Fisch et al., 2017).

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Marine Mollusks

Biology Food and feeding: These animals make use of their radula for feeding on such things as sipunculids and nemerteans. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults.

 

Kulolide 2          Kulolide 3

Compound(s) and Activities Antiangiogenic activity: At a tested concentration of 200 µg, the methanolic extracts of this species exhibited a fairly higher degree of antiangiogenic activity with an inhibitory percentage (60.5%) of the VEGF-induced neovascularization (Gupta et al., 2014). The significant antiangiogenic activity evinced by the extract of this species merits further investigation for use in treating ocular neovascular diseases.

Bufonaria echinata (Link, 1807) (=Bursa spinosa)

Kulokainalide-1

Bufonaria crumena (Lamarck, 1816)

Order: Littorinimorpha Family: Bursidae Common name: Purse frog shell Distribution: Indo-West Pacific: East and South Africa to Melanesia; north to the Philippines and south to Queensland Ecology: It is a benthic species inhabiting submerged rocks; depth range 0–50 m. Description: Shell of this species is moderate in size, broad, and ovate; apex is pointed; and sculpture is composed of nodulose spiral threads. Body whorl has rows of short sharp nodes, and remaining whorls have a single spiral row of tubercles; two finlike varices are seen on both sides; and varices have sharp nodes at regular intervals. Aperture is ovate, outer lip is expanded and supported by a varix, inside of outer lip is toothed, columella is denticulate at the base, and siphonal canal is short and twisted. Color of the shell is light brown with dark brown spots close to the nodes, and aperture and lips are white slightly orange. It grows to a maximum length of 9 cm.

Order: Littorinimorpha Family: Bursidae Common name: Spiny frog shell Distribution: Western Indian Ocean; India; Red Sea; off Madagascar; off the Philippines and China Ecology: This benthic, reef-associated species largely inhabits the intertidal zones of sandy coastal waters. Description: Shell of this species is somewhat dorsoventrally depressed, and whorls are slightly angulated. Strong spines are present. Each whorl has a pair of varices, which develop into strong, elongated, outwardly directed spines at rather irregular intervals. There is also a single spine adjacent to the posterior canal; this spine is directed backwards. In addition to the spines on the varices, there are one or two regular, spiral rows of widely spaced, short, pointed, spinelike tubercles. Edge of the outer lip presents a frilled appearance owing to the presence of strong, irregular, transverse teeth. Color of the shell is uniformly smoky brown, and shell size is between 50 mm and 85 mm. Biology Food and feeding: These animals are active predators and appear to feed on polychaetes that they anaesthetize with acidic saliva through their extensible, distally flattened probosces. Reproduction: As in B. crumena.

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Compound(s) and Activities Antioxidant activity: The methanolic extract of this species showed antioxidant activity. The value of DPPH radical scavenging activity was found to be 39.43% at 10 mg/ml, whereas the butylated hydroxytoleune (BHT) and ascorbic acid showed 63.67% and 59.8% respectively (Subhapradha et al., 2013).

Biology and Ecology of Pharmaceutical Marine Mollusks

Charonia lampas (Linnaeus, 1758)

Bufonaria rana (Linnaeus, 1758) (=Bursa rana)

Order: Littorinimorpha Family: Bursidae Common name: Common frog shell Distribution: Indo-Pacific: from Indonesia to Polynesia; north to Japan and south to southern Queensland Ecology: This benthic species occurs on mud or muddy-sand bottoms of the continental shelf; usually at the lowest tides near seagrass meadows; depth range 42–166 m. Description: Shell of this species is moderately large and solid; it is dorsoventrally compressed; and spire is raised. Varices on both sides are finlike with two to three small spines, sculptured with granulated spiral ribs. Body whorl bears two rows of spiral cords with fine nodes and one row on penultimate whorl; rest of the shell surface has granulose spiral threads and spinous nodes. Aperture is slightly ovate; and outer lip is denticulate. Columella is smooth and denticulate towards base. Siphonal canal is short. Color of the shell is light brown and aperture is white. It grows to a maximum length of 9 cm. Biology Food and feeding: It appears to feed on tube worms. It has an extendible proboscis and large salivary gland that are probably used to anaesthetize the worms in their tubes, and the worms are then sucked out and swallowed whole. Reproduction: As in B. crumena. Compound(s) and Activities Antibacterial activity: The whole-body methanol extracts of this species showed 63% inhibition against 40 species of marine biofilm bacteria (Anon., https​ ://ww​ w.the​ freel​ibrar ​y.com ​/ Pote​ntial​+anti​m icro​bial+​a ctiv​ity+o​f+mar​ ine+molluscs+fr​om+tu​ticor​in%2c​...-a​01331​081).​

Order: Littorinimorpha Family: Ranellidae Common name: Mediterranean triton, pink lady Distribution: Mediterranean Sea, North Sea, Atlantic Ocean, and Indian Ocean Ecology: It occurs in low tide areas to about 160 m. Description: Shell of this species is large, solid, and glossy, with a tall pointed spire and an angulated profile. It has 7–8 whorls meeting at shallow sutures. Last whorl is large and occupies about two thirds of shell height. Whole shell surface is covered with small spiral ridges, but up to ten on the last whorl and two on each whorl in the spire are much bigger than the others and are also nodose. There are varices at 120° intervals. Each varix consists of a prominent swelling across the whorl with a sharp, undercut edge on the side facing down the spiral. Aperture occupies a little more than half of shell height. Columella is fluted with ridges, one large one adapically. Outer lip is with paired short ridges internally. Shell is white with brown blotches, especially near sutures, on the inner folds of the outer lip and at the base of the columella. Height of the shell is 400 mm and width 150 mm. Biology Food and feeding: It is a predator on mussels, starfish, and holothurians. The triton grips its prey with its muscular foot and uses its toothy radula to saw through the starfish’s armored skin. Once it has penetrated, a paralyzing saliva subdues the prey, and the snail feeds at leisure. They ingest smaller prey animals whole without troubling to paralyze them. Reproduction: Tritons are not hermaphrodites; they have separate sexes and undergo sexual reproduction with internal fertilization. The female deposits white capsules in clusters, each of which contains many developing larvae. The larvae are planktonic, and they drift in open water for up to three months. Compound(s) and Activities Enzymes (exoglycosidases): This species has been reported to produce the enzymes exoglycosidases, which are essential tools for the study of the biological activity of sugar chains since they can specifically remove sugars from intact glycoproteins and glycolipids (Anon., http:​//www​4.mpb​io.co​m /eco​ m/doc​s/pro​ddata​.nsf/​(webt​ds2)/​32126​).

65

Marine Mollusks

Crepidula fornicata (Linné, 1758)

Order: Littorinimorpha Family: Calyptraeidae Common name: Common slipper shell, common Atlantic slippersnail, boat shell, quarterdeck shell, fornicating slipper snail, Atlantic slipper limpet Distribution: Native to the western Atlantic Ocean, specifically the Eastern coast of North America; cosmopolitan species; Britain and Ireland Ecology: It is usually found intertidally, infralittorally, and circalittorally; it can tolerate a wide range of environmental conditions; populations are particularly well developed in wave-protected areas such as bays, estuaries, or sheltered sides of wave exposed islands, sometimes living stacked on top of one another, on rocks, horseshoe crabs, shells, and dock pilings; depth range 0–70 m. Description: Shell of this species is oval, up to 5 cm in length, with a much reduced spire. Its large aperture has a shelf, or septum, extending half its length. Shell is smooth with irregular growth lines and is white, cream, yellow, or pinkish in color, with streaks or blotches of red or brown. This species is commonly found in curved chains of up to 12 animals. Large shells are found at the bottom of the chain, with the shells becoming progressively smaller towards the top. Biology Food and feeding: It is an active suspension feeder, generating a water current through the mantle cavity by ciliary action and trapping food particles (phytoplankton and particulate organic food) on a mucous sheet lying across the front surface of the gill. Reproduction: It is a protandrous hermaphrodite (animals start their lives as males and subsequently may change their sex and develop into females). Although breeding can occur between February and October, peak activity occurs in May and June, when 80%–90% of females spawn. Compound(s) and Activities Antibacterial activity: The acidic extracts of this species showed growth inhibition diameter of less than 7 mm against M. luteus and V. anguillarum (Defer et al., 2009). Antiviral activity: The organic extracts of this species showed antiviral activity with 46.8% inhibition at a protein concentration of 110 µg/mL (Defer et al., 2009).

Erronea errones (Linnaeus, 1758) (=Cypraea errones)

Order: Littorinimorpha Family: Cypraeidae Common name: Wandering cowry, erroneous cowry Distribution: East Indian Ocean: South India, Andaman Islands, Madagascar, and Tanzania; West Pacific Ocean: Indonesia, Malaysia, Philippines, New Caledonia, Samoa, and Australia Ecology: This benthic species is usually found under rocks or stones in shallow tropical waters at low tide. Description: Shell of this species is cylindrical. Upperside variable patterns with one or two brown spots at the front tip of the shell, sometimes no spots. Underside is without colored “teeth.” In living cowries, the papillose greenish mantle serves as camouflage. Shell reaches a maximum length of 4.5 cm. Biology Food and feeding: It is herbivorous, feeding on algae. Reproduction: In India, the breeding of this species was observed from September to April. The newly laid egg mass is yellowish in color. The number of eggs varies from 30 to 70 per capsule. The eggs are yellowish brown. The newly hatched veliger larvae, which are pale brownish in color with reticulate markings, escape through the distal end of the capsule (Anon., http:​//epr​ints.​cmfri​.org.​in/68​95/1/​033-C​URREN​ T_SCI​ENCE-​3.pdf​). Compound(s) and Activities Antimicrobial activity: The crude methanol extracts of this species displayed antimicrobial activity against S. aureus, Streptococcus pyrogenes, A. niger and C. albicans and the values of inhibition zones (mm) were 3, 3, 5, and 1, respectively (Anand and Edward, 2002).

Cypraea tigris (Linnaeus, 1758)

Order: Littorinimorpha Family: Cypraeidae Common name: Tiger cowry

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Distribution: Indo-Pacific: from the eastern coast of Africa to Micronesia and Polynesia; Coral Sea and around the Philippines; from Northern New South Wales to northern Western Australia, as well as Lord Howe Island; and east coast of Africa including Madagascar Ecology: This benthic species is found between depths of 10 and 40 m. It is often associated with live coral colonies, such as the table-forming Acropora, being either found on the reefs themselves or the sandy sea bottom nearby. Description: Shell of this species is roughly egg-shaped and dextral and is large, glossy, and heavy. It measures up to 16 cm in length; the upper or dorsal side is white, pale bluishwhite, or buff, and densely covered with dark brown or blackish barely circular spots. Shell surface is notably effulgent. There is sometimes a blurred red line along the length of the shell at the midline on the dorsal surface. Lower margins are rounded (that is, there is no sharp margin between the upper and lower surfaces of the shell, as is found in some other cowries). Ventral side is white or whitish, and the shell opening is lined with toothlike serrations. These animals can be kept in aquariums and are in demand for rock-type aquariums. Biology Behavior: Tiger cowries are seldom seen with their mantles out during the day and are usually in hiding during daylight. On rare occasions, they are seen out in the open with the mantle retracted. Food and feeding: They are predators, and their diet consists of sponges and soft corals and other marine organisms. They are nocturnal and feed at night. Predators: These animals are preyed upon by some species of fish and octopus, which bite through their shells and cone shells. Reproduction: The tiger cowrie is either male or female, and after mating, the female will lay the eggs and cover them with her foot. Once the eggs hatch, they enter a planktonic stage and then develop into young adults. Interestingly, once a cowrie has reached its adult size, the shell stops growing. Compound(s) and Activities Antiatherosclerotic activity: This species has been reported to have bioactive compounds that are potential antiatherosclerotic substances (Sarizan, 2013). Further intensive research is, however, needed on this aspect.

Biology and Ecology of Pharmaceutical Marine Mollusks

Distribution: Indo-West Pacific: From East and South Africa (including Madagascar, but not the Red Sea or the Persian Gulf), to the eastern Polynesia; north to Japan and south to New South Wales, Australia Ecology: It dwells under boulder and stones and also shelters in caverns on the outskirts of coral reefs; it is found in low intertidal zones to shallow sublittoral depths; it is mainly active during the nocturnal period. Description: Shell outline of this species is oblong or nearly elliptical. Spire is barely distinguishable dorsally. Aperture of the shell is very narrow and relatively long. Both the inner and outer lips are ornamented with arrays of small teeth. Dorsal side of the shell is convex or bent. Ventral side of the shell is typically flattened and sometimes slightly concave. Shell surface is notably effulgent (shiny), as if it had been well polished. Color of the shell is generally cream to light fawn dorsally, with shades of brown. Ventral side of the shell is colored cream to gray. Common name “Arabian cowry” is based on a dense and irregular pattern of thin longitudinal brown lines that are sometimes interrupted by empty spaces, giving an appearance that is considered to be similar to that of Arabic script. Shell size may vary from 5.0 to 10.5 cm. Biology Food and feeding: Cowries eat a wide variety of things, from algae and sponges to scavenging and carnivorous cowries that eat other snails. Nothing is known about its feeding habits, although it may feed primarily on diatoms. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Anticancer activity: The organic extracts of this species displayed anticancer activity against HepG2 cancer cell line. The percentage of cell viability was decreased with increasing concentration, that is, 74.14% at 250 μg/ml, 56.93% at 500 μg/ml, and 45.34% at 750 μg/ml concentrations of the extract, and the percentage of toxicity was observed as 25.86% of inhibition at 250 μg/ml, 43.06% at 500 μg/ml, and 54.65% at 750 μg/ml concentrations (Subavathy et al., 2015).

Monetaria moneta (Linnaeus, 1758) (=Cypraea moneta)

Mauritia arabica (Linnaeus, 1758) (=Cypraea arabica)

Order: Littorinimorpha Family: Cypraeidae Common name: Arabian cowry

Order: Littorinimorpha Family: Cypraeidae Common name: Money cowry

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Marine Mollusks

Distribution: Indo-Pacific: East and South Africa, Madagascar, the Red Sea, and the Persian Gulf; Maldives, eastern Polynesia, Galapagos, Clipperton and Cocos islands off Central America; southern Japan, Midway, and Hawaii; and northern New South Wales and Lord Howe Island Ecology: It lives in intertidal rocky areas and shallow tide pools among seaweed, coral remains, and empty bivalve shells; found on and under rocks in shallow water and on exposed reefs at low tide. Description: Shell of this species is irregular and flattened, with very calloused edges, and is roughly subhexagonal. Shell color is pale (from white to dirty beige), but the dorsum seems transparent, often greenish gray with yellowish margins, with sometimes darker transverse strips and a fine yellow ring. Opening is wide and white, with pronounced denticules. Mantle of the live animal is mottled with black and dirty white. Two shell morphs, distinguished by the presence or absence of knobs, occur in this species: one type is with four knobs, two posterior and two posterior-lateral; and the other type is smooth and without knobs. These shell forms are further distinguished by the presence or absence of yellow pigment on their ventral surface. Thus, two varieties in each morphological type are apparent: yellow and white varieties of the smooth and knobby shells (Renaud, 1976). Shell grows to a maximum size of 3 cm. Biology Food and feeding: The most preferred alga of the smooth morphs is the red alga Jania capillacea, the most abundant species in intertidal areas; and that of the knobby morphs is the blue-green alga Schizothrix calcicola, a common subtidal species (Renaud, 1976). Reproduction: It is gonochoric and a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antibacterial activity: The shell powder extract of this species showed antibacterial activity against human pathogens, namely Micrococcus sp., P. vulgaris, and Salmonella abory. Among these, P. vulgaris showed the maximum zone of inhibition (15 mm size) against 5% w/v concentration, followed by Micrococcus sp. (12 mm) and S. abory (10 mm) against the same concentration (Immanuel et al., 2012). Wound healing: The wound-healing effect of the shell powder of this species was found to be very effective in albino rats (Immanuel et al., 2012). It is suggested that the processed shell powder of this species can be used as an alternative medicine. Antipyretic effect: The shell powder extract of this species showed an antipyretic effect in albino rats. In the treated rats, the body temperature became normal within a short duration (3 h) (Immanuel et al., 2012). Others: The burned shell powder of this species has been reported to cure asthma (Ahmad et al., 2018).

Ficus ficus (Linnaeus, 1758)

Order: Littorinimorpha Family: Ficidae Common name: Paper fig shell, fig snail Distribution: Indian Ocean and West Pacific. Ecology: It is a benthic, subtidal species occupying muddy and sandy substrates; depth range 0–176 m. Description: Shell of this species is medium sized and thin, spire is not elevated, body whorl is inflated with deep suture, and sculpture is composed of thin axial ridges intercepted by prominent spiral ridges forming a reticulate appearance. Aperture is wide and outer lip is slightly thickened towards the anterior end. Ground shell color is light brown with spiral bands of white and scattered dark brown blotches. Shell may reach 14.5 cm in length. Biology Food and feeding: The individuals of this species are primarily polychaete (Onuphis sp. and Oiopatra sp.) feeders. Their teeth and feeding structures suggest that they do not eat large prey. Reproduction: Varied sex ratios observed would indicate the existence of egg-laying migration in this species. In this species, peaks of copulation and egg laying have been observed from November to January and January to February, respectively. Laid egg capsules are translucent white and rectangular, about 0.5 to 1 cm long without a stalk. Collection of fewer females during the reproductive season (October–February) would signify that a copulated female might migrate to sites with hard substrata to deposit her egg capsules for firm attachment (Liu and Wang, 1999). Compound(s) and Activities Antibacterial activity: The organic extracts of this species showed antibacterial activity against human pathogenic bacteria, and the values of inhibition zone are given below. Inhibition of Zone (mm) E. coli 2.8

S. typhi

S. paratyphi

V. parahaemolyticus

3.4

2.9

4.8

Source:  Jayanthi et al. (2016).

S. aureus 4.7

68

Antifungal activity: The organic extracts of this species have shown antifungal activity against Fusarium spp. with the inhibition zone value of 7.0 mm (Jayanthi et al., 2016). Kanchana et al. (2014) reported that the methanol extract of this species was found to moderately inhibit the growth of the fungal species Aspergillus fumigatus with a 4 mm zone of inhibition. Hemolytic activity: The methanol extracts of this species when tested with the chicken red blood cells showed hemolytic activity at a concentration of 7.6 µg (Kanchana et al., 2014).

Lobatus gigas (Linnaeus, 1758) (=Strombus gigas)

Order: Littorinimorpha (Neotaenioglossa)  Family: Strombidae Common name: Queen conch, pink conch Distribution: Native to the tropical northwestern Atlantic, from Bermuda to Brazil Ecology: It is a benthic species having a depth range 2–73 m. Description: Adult animal of this species has a very large, solid, and heavy shell, with knoblike spines on the shoulder, a flared thick outer lip, and a characteristic pink-colored aperture. Flared lip is absent in younger specimens. Spire is relatively large. Sculpture is of sharp knobs along shoulder. Color of the shell is pale tan with thin brown periostracum. Internal shell color is deep pink. Shell reaches up to 35 cm in length. External anatomy of the soft parts of this species comprises a long snout, two eyestalks with well-developed eyes, additional sensory tentacles, a strong foot, and a corneous, sickle-shaped operculum. This species is highly commercial. Biology Food and feeding: L. gigas is a specialized herbivore that feeds on macroalgae (including red algae, such as species of Gracilaria and Hypnea), seagrass, and unicellular algae. Intermittently, it also feeds on algal detritus. The green macroalgae Batophora oerstedii is one of its preferred foods. Reproduction: Adult queen conches migrate to shallow, warmer inshore waters to mate and lay their eggs. The peak reproduction period is from April to August. They lay between 180,000–460,000 eggs in gelatinous strings, some as long as 25 m. Females may spawn many times during a reproductive season. Planktotrophic (feeding) larvae emerge and

Biology and Ecology of Pharmaceutical Marine Mollusks

travel long distances in the water column. After 18 days, the swimming veliger shifts to a swimming/crawling stage that allows it to move along the substratum and find an appropriate place to settle and metamorphose (Anon., https​://ww​w.sms​.si. e​du/ir​lspec​/Stro​mbus_​gigas​.htm)​. Compound(s) and Activities Antiviral activity: The unidentified bioactive macromolecules extracted from the organic extracts of this species showed antiviral activity (Dang et al., 2011).

Margistrombus marginatus (Linnaeus, 1758) (=Strombus marginatus)

Order: Littorinimorpha Family: Strombidae Common name: Marginated conch Distribution: Andaman Sea, at the southern tip of India and the Strait of Malacca Ecology: It is found on sandy shores and near seagrasses. Shell may also be covered with encrusting organisms. Description: Shell of this species is smooth and moderately elongate. Adults normally have ten complete whorls. Aperture is narrow and smooth. Columella is polished and callus white, faintly wrinkled above and below. Outer lip is curled and extends up to the main shell, forming a beaklike structure. Color of the shell is pale chestnut or fawn, slightly mottled with white; the margin of the aperture and the pillar are white; and aperture is yellow. Shell size varies between 40 mm and 75 mm. Biology Food and feeding: It feeds mainly on minute algae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antibacterial activity: The methanol:water (1:1) extracts of this species exhibited antibacterial activity against more than 60% of marine biofilm bacteria (Anon., https​://ww​w.the​ freel​ibrar ​y.com ​/ Pote​ntial​+anti​m icro​bial+​a ctiv​ity+o​f+mar​ ine+molluscs+fr​om+tu​ticor​in%2c​...-a​01331​08179​).

Marine Mollusks

Harpago chiragra (Linnaeus, 1758) (=Lambis chiragra)

Order: Littorinimorpha Family: Strombidae Common name: Chiragra spider conch Distribution: Indo-Pacific: From Aldabra Atoll, Chagos, Mauritius, Mozambique, Sri Lanka, and the Gulf of Bengal to eastern Polynesia; Taiwan and southern Japan, and south to New Caledonia and Australia Ecology: It lives in coral reef areas and seagrass beds; littoral and sublittoral zones; and tidal pools and low tide levels to a depth of around 25 m. Description: H. chiragra has a very thick, robust, and heavy shell, with a distinct anterior notch. Its most prominent characteristic features are the six long, curved marginal digitations expanded from the flaring, thick outer lip and canals. Columella and aperture are lirate. Shell length varies between 8.5 cm and 32 cm. Biology Food and feeding: It is a herbivorous gastropod, feeding on benthic filamentous algae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antibacterial activity: The methanol extract of this species showed activity against V. cholerae and S. paratyphi with inhibition zone diameter values of 7–10 mm and more than 10 mm, respectively (Kanchana et al., 2014).

Lambis lambis (Linnaeus, 1758)

Order: Littorinimorpha (Neotaenioglossa) Family: Strombidae Common name: Common spider conch

69

Distribution: Indo-West Pacific: Aldabra, Kenya, Madagascar, Mauritius, Mozambique, the Persian Gulf and the Red Sea, Seychelles, Tanzania, Micronesia, eastern Melanesia, Taiwan, southern Japan, and northern Australia Ecology: This sea snail lives in mangrove areas, as well as reef flats, muddy areas, and coral-rubble bottoms in shallow water from low tide levels to depths of 24 m; usually found in association with red algae; shallowly burrows in sand or gravel. Description: L. lambis has a very large, robust, and heavy shell. One of its most striking characteristics is its flared outer lip, ornamented by six hollow marginal digitations (spines). Three anteriormost digitations are short and posteriorly bent in male individuals, and longer and dorsally recurved in females. Spines on the shell improve stability and prevent the snail from toppling over as it hops. Color of the shell is highly variable, being white or cream externally and often presenting brown, purplish, or bluish-black patches. Interior shell is glazed and may be pink, orange, or purple. Shell opening is pearly and pinkish with orange or yellow tints. Part of the body of the animal is olive brown with white spots. It has large eyes on long stalks and a thick siphon. It has a curved, knife-shaped operculum attached to a long strong foot. This is used by the animal to “hop” along the surface. Maximum shell length for this species is up to 29 cm. Biology Food and feeding: It predominantly feeds on sand grains, polychaetes, bivalves, and small crustaceans. Reproduction: In this species, sexes are separate. Usually a pair is involved in mating, although as many as three or four males have been associated with a spawning female. Females produce between 100,000 and 500,000 eggs, which are very small and covered by a thick rounded jelly sheath. It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. In Indonesian waters, the sex ratio of males and females was found to be 1.0:1.2. Spawning occurred throughout the year, with peak spawning from January until March (Widyastuti and Aji, 2016). Compound(s) and Activities Cytotoxic and genotoxic activities: The alkaloids, terpenes, and proteins present in the mucus of this species showed cytotoxic and genotoxic effects (See et al., 2016). Antibacterial activity: The extracts of body tissue of this species showed antibacterial activity against eight bacterial pathogens, namely B. subtilis, E. coli, S. typhi, K. pneumoniae, Shigella flexneri, P. aeruginosa, S. aureus, and V. cholera. Of all the fractions tested, the methanolic extract showed the maximum activity (Vimala and Thilaga, 2012). According to Rohini et al. (2012), the water extract of this species was found to be active against P. aeruginosa, P. vulgaris, and Klebsiella aerogenes. On the other hand, the growth of P. aeruginosa, Flavobacterium columnare, and S. aureus was effectively controlled by the methanolic extracts of this species.

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Biology and Ecology of Pharmaceutical Marine Mollusks

Tibia curta (Sowerby II, 1842)

Coriocella nigra (Blainville, 1824) (=Chelyonotus semperi)

Order: Littorinimorpha Family: Strombidae Common name: Indian tibia Distribution: From Persian Gulf to Bay of Bengal Ecology: Most live in off shore waters where there is plenty of sand; depth range 5–50 m. Description: Shell of this species has a fusiformly towershaped projection; spire very much tapers to a point; canal is straight; and 15 quite level whorls are somewhat flattened. First few whorls are longitudinally ribbed while the rest are smooth, and columella has a callous. Outer lip is irregular with several short projections; and canal is rather short and curved backwards. Shell color is light reddish/brownish yellow or brown, with a rather broad pale chestnut/brown band close to the suture of the whorls. Columella and interior of aperture is white. Size of the shell varies between 120 mm and 185 mm. Biology Food and feeding: It is presumed to be a herbivorous to omnivorous gastropod which swallows quantities of sand and digests algae and detritus within, as well as grazing on algae. Reproduction: Not reported Compound(s) and Activities Antimicrobial activity: The extract of this species possessed protein, amino acid, and carbohydrate. The diameter of inhibition zone (mm) as antibacterial activity recorded for the tested bacterial species is given below:

Escherichia coli

18.3

Pseudomonas aeruginosa Proteus mirabilis Klebsiella oxytoca

22.3 14.6 22.6

Serratia liquefaciens

22.3

The minimal inhibitory concentration (MIC) of the above extract was found to be 10 mg/mL for all bacterial species tested except P. mirabilis, which showed a value of 30 mg/mL (Degiam and Abas, 2010).

Order: Littorinimorpha Family: Velutinidae Common name: Velet snail, Velutin snail Distribution: Indo-Pacific Ecology: It inhabits rocky habitats of intertidal and subtidal zones, at depths of up to 15 m. Description: This is a large, black species covered with broad tubercles. Cephalic tentacles are speckled with white. Shell of this species is lightweight and its whorls are uniformly rounded and smooth except for irregular growth lines. Aperture is large, columella is smooth, and outer lip is thin and smooth. Color of the shell is translucent white. Shell length varies from 10 mm to 30–40 mm. Biology Food and feeding: It is a predator, feeding on colonial ascidians using its radula, which reduces the prey to fine food particles. Reproduction: It is a gonochoric species. The penis, proportionally very large compared to the rest of the body, opens in the right front part of the head. The egg mass which is black in colour contains hundreds of eggs. Compound(s) and Activities Anticancer activity: A series of pentacyclic alkaloids have been isolated from this prosobranch mollusk. Among these compounds, only kuanoniamine A showed weak growth inhibitory activity against KERATIN-forming tumor cell line HeLA (KB) cancer cells (GI50 = ∼4 μM) (Ciavatta et al., 2017).

Kuanoniamine A Ciavatta et al. (2017) reported that two members of the staurosporine, viz. 4’‐N‐demethyl‐11‐hydroxystaurosporine and 3,11‐dihydroxystaurosporine, isolated from this species displayed anticancer activity against a minipanel of cancer cell lines with GI50 values ranging between 4 and 130 nM.

71

Marine Mollusks

tinged with violet. Background color varies from white to yellow to bright orange-red. Cephalic tentacles are flecked with white. Underside of the foot usually has faint orange-brown flecks. It may derive its color primarily from the tunicates it eats. It reaches a maximum size of 2.8 cm. Biology Food and feeding: It is a carnivore, feeding on tunicates. Reproduction: Not discusses as it is an unidentified species. 4′‐N‐​demet​hyl‐1​1‐hyd​roxys​tauro​spori​ne

 

Compound(s) and Activities Antitumor/cytotoxic activity: The hexacyclic pyrrole alkaloids, lamellarins A–D, of this species have been isolated. Among these compounds, lamellarin D showed promising antitumor activity against human cell lines (HU) and murine cell lines (MU) tumor cell lines. It induces apoptotic cell death through multitarget mechanisms, including inhibition of topoisomerase. This compound may serve as a lead in the search for treatments against chemoresistant cancer cells (Mayer and Gustafson, 2006; Fan et al., 2008).

3,​11‐di​hydro​xysta​urosp​orine​

Lamellaria sp. Lamellarin D

Littorina littorea (Linnaeus, 1758) [1]

Order: Littorinimorpha Family: Velutinidae Common name: Not designated as it is an unidentified species. Distribution: Indo-Pacific; Big Island, Maui, Oahu, French Frigate Shoals, and Lisianski Habitat: It lives in moderately protected to moderately exposed rocky habitats with rubble, dead coral and green alga, Halimeda kanaloana beds at depths of 1

85

Marine Mollusks

mm per week, reaching shell lengths of 40–50 mm within five months post-settlement and >60 mm at 1 year (Anon., CABI, https​://ww​w.cab​i.org​/isc/​datas​heet/​66682​). Compound(s) and Activities Anticancer activity: The organic extracts of this species showed anticancer activity against SiHa-cervical squamous cell carcinoma, CaOV-ovarian adenocarcinoma, MIA PaCapancreatic carcinoma, RD 64-rhabdomyosarcoma, EJ-urinary bladder carcinoma, and Lep-nontumor human lung cell lines (Benkendorff et al., 2015). Antibacterial activity: The hemolymph which contains proline rich peptides of this species was found to inhibit the Gram-positive S. aureus and Gram-negative K. pneumoniae (Benkendorff et al., 2015). The hemolymph collected from the foot of this species showed the presence of prorich peptides that exhibited strong antimicrobial activities against tested microorganisms, including Gram-positive and Gram-negative bacteria (Dolashka et al., 2011). Antiviral activity: The hemolymph, which contains hemocyanin, of this species has been reported to inhibit the replication of Epstein-Barr virus (EBV) at 1 μg/mL and Herpes simplex virus type 1 at 200 μg/mL (Benkendorff et al., 2015). Dang et al. (2015) reported that the glycosylated functional unit of hemocyanin/RtH2 of this species displayed antiviral activity against respiratory syncytial virus, HSV-1a and HSV2, and EBV. Antioxidant activity: The dry-matter methanol extracts of this species (collected from polluted and nonpolluted areas) showed DPPH radical scavenging activity with 62.3% and 30.3%, respectively (Moncheva et al., 2011). Wound healing and anti-inflammatory activity: The hemocyanin (RtH) content of this species induced strong humoral immune response in mice (40, 100, and 250 μg/mouse), and this compound could be used as an adjuvant. The amino acids of this species have been reported to accelerate skin wound healing via enhancement of dermal and epidermal neoformation. Treatment with amino acids at a concentration of 0.3 mg/kg, twice a day, enhanced healing of wound and skin burns in Wistar rats. Further, the lipid extract (0.2 mg/kg, twice a day), containing polyunsaturated fatty acids, Vitamin E, sterols and aromatic compounds, was also found to be very efficient in healing induced skin burns in Wistar rats (Benkendorff et al., 2015; Badiu et al., 2010; Ahmad et al., 2018).

Distribution: Western Pacific: Southeast and Northeast Asia; Malaysia, Singapore, and Indo-China Ecology: It is an intertidal species, living on rocky shores. Description: This species has been found to be useful as an indicator of the environmental contamination levels of arsenic, copper, and zinc (Wikipedia). No other information is available. Biology Food and feeding: It is a carnivorous gastropod, feeding on mussels. It feeds on prey by boring through their shells, followed by extracellular digestion and suction of the nutrientrich fluid of the prey’s body tissues. Reproduction: Sexes are separate in this species, and fertilization is internal. The reproductive cycle can be classified into five successive stages: early active, late active, ripe, spawning, and recovery. Spawning of females occurred from early July to August, when the seawater reached above 24.8°C. Spawning of males occurred from early June to August in water above 22.8°C. Minimum size for sexual maturity of both sexes was above 10.0 mm in shell height. Each egg capsule was a cylinder or spindle in shape, 4–6 mm in length and 1–2 mm in width. Colors of newly spawned egg capsules showed yellowish white or pale yellow, while those of veliger larvae showed pale black, and released larvae or dead egg capsules showed black-violet. The fecundity in an egg capsule ranged from 70 to 91 eggs (Lee, 1999). Compound(s) and Activities Anticancer activity: The ethanol extracts of this species showed anticancer activity against human leukemia HL-60 and human lung cancer A-549- MTT cell viability (Benkendorff et al., 2015).

Phycothais reticulata (Quoy and Gaimard, 1833)

Reishia clavigera (Küster, 1860) (=Thais clavigera)

Order: Neogastropoda Family: Muricidae Common name: Rock-shells, Korean common dogwhelk

Order: Neogastropoda Family: Muricidae Common name: Knobbly rock-shell Distribution: Red Sea, Australia, and Tasmania Ecology: It lives intertidally and subtidally amongst rocks and seaweed, especially in moderately exposed environments. Biology: In this species, shell shape varies. Some shells bear black-tipped nodules, but these are lacking in worn shells. Dark brown forms elongate dashes along the spiral sculpture. It reaches a maximum size of 12 mm.

86

Biology and Ecology of Pharmaceutical Marine Mollusks

Biology Food and feeding: Not reported. Reproduction: Not reported. Compound(s) and Activities Antibacterial activity: The CHCl3 content of the egg mass of this species inhibited human pathogenic bacteria (Staphylococcus aureus, E. coli, and P. aeruginosa) at 10 mg/mL (Benkendorff et al., 2015).

Drupella fragum (Blainville, 1832)

Antioxidant activity: Three new bromoindoles, 6-bromo-5-hydroxyindole, 6-bromo-4,5-dihydroxyindole, and 6-bromo4,7-dihydroxyindole, isolated from the midintestinal gland of this species showed antioxidant activity. Among these compounds, compound 1 was found to have as strong an antioxidative potency as BHT (Ochi et al., 1998).

  

     

 

6-bro​mo-5-​hydro​xyind​ole  6​-brom​o-4,5​-dihy​droxy​indol​e

6-b​romo-​4,7-d​ihydr​oxyin​dole

Drupella margariticola (Broderip, 1833) (=Drupa margariticola) Order: Neogastropoda Family: Muricidae Common name: Not designated Distribution: Pacific Ocean. Ecology: This benthic species occurs in a range of habitats such as lagoons, pinnacles, and seaward reefs. Description: Shell of this species is small with a size of about 4 cm. No other information is available. Biology Food and feeding: It is a coral-eating gastropod and it uses its a graterlike feeding organ (radula) to scrape soft coral tissues away from the hard skeleton. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antimicrobial activity: Three new indolequinones, 6-methoxyindole-4,7-quinone, 5-methoxyindole-4,7-quinone, and 5-methylindole-4,7-quinone, isolated from the midintestinal gland of this species showed antimicrobial activity. Among these compounds, compounds 1 and 3 exhibited moderate antimicrobial activities against Staphylococcus aureus, B. subtilis, and E. coli with MIC = 6.25 ∼ 50 μg/mL (Fukuyama et al., https://doi.org/10.1002/chin.199849297).

                6-met​hoxyi​ndole​- 4,7-​quino​ne 5-​ m etho​ x yind​ o le- 4​ ,7-qu​ inone​

Order: Neogastropoda Family: Muricidae Common name: Shouldered castor bean Distribution: Red Sea, Indian Ocean along Aldabra, Chagos, Madagascar, the Mascarene Basin, the Seychelles, Tanzania, and in the Western Pacific Ocean and Japan Ecology: It is found on rocks covered with oysters at low tide mark. It is a coral-associated species. Biology: Shell size of this species varies between 14 mm and 40 mm. No other information is available. Biology Food and feeding: It is a corallivore, feeding on live coral tissue. Drupella prefer to feed on fast-growing species with complex, branching growth forms such as Acropora and Pocillopora. Reproduction: As in D. fragum. Compound(s) and Activities Antibacterial activity: The active compound diterpenoid acylglycerol isolated from this species exhibited broad spectral

87

Marine Mollusks

antibacterial activity against S. typhimurium, V. cholerae, and B. subtilis, with inhibitory zone diameter values of 8 mm, 8 and 8 mm, respectively at a concentration of 50 μg (Chellaram and John, 2014).

Acylglycerol The mucus-associated bacteria of this species have been reported to show antagonistic activity and inhibited the human pathogenic bacteria. These bacterial strains exhibited full or complete degree of inhibition against E. coli (Chellaram et al., 2005). Antinociceptive activity: The 100% acetone fraction of this species showed significant analgesic action. At 25 and 100 mg kg−1 (p.o.), this extract exhibited significant writhing inhibition of 65% and 78.57%, respectively, against acetic acid–induced abdominal constrictions (Chellaram and Edward, 2009a). Anti-inflammatory activity: At the concentration of 50 and 100 mg/kg (p.o), the 100% acetone extract of this species showed significant decrease in paw thickness, 36.5% and 72.9% respectively, at the 5th hour of the experiment (Chellaram and Edward, 2009b; Ahmad et al., 2018).

off-white or gray; aperture is cream and often pale yellow on the edge. Shell has a maximum length of 120 mm. Biology Food and feeding: It is a carnivorous species, feeding mainly on wild fish. Reproduction: The egg masses of this species are predominantly deposited on the shoreward side of the pilings. The mean number of egg capsules in a single group within an egg mass ranged from 13 to 72. The number of eggs per capsule ranged from 3,519 to 5,908. From the eggs, stage 1 (veliger stage) appeared, followed by stage 2, in which the shell shows approximately two full shell whorls with visible growth markings at the shell beak. Shell morphology changes considerably throughout development (Noble, 2014). Compound(s) and Activities Anticancer activity: The egg-mass extracts of this species have been reported to induce necrosis in HT29 colorectal cancer cell line and induce apoptosis in Jurkat cells (Pati et al., 2015). Ciavatta et al. (2017) reported that the indole-based compound tyrindoleninone isolated from the egg-mass extract of this species has shown activity against human colon cancer cells with GI50 values of >100 μM.

Dicathais orbita (Gmelin, 1791) Tyrindoleninone The indole-based compounds, 6-bromoisatin and tyrindoleninone, of this species showed anticancer activity and induced apoptosis in several cancer cell lines, both in vitro and in vivo. These novel bioactive compounds would exert selective cytotoxicity towards the reproductive cancerous cells while having minimal or no effect on the reproductive primary cells (Edwards, 1967).

Order: Neogastropoda Family: Muricidae Common name: White whelk, Australian dogwhelk, cartrut shell Distribution: In Australia, from Fraser Island, Queensland, to North West Cape, Western Australia, including Tasmania; also New Zealand and Lord Howe Island Ecology: It occurs on rock platforms and rocky shores, in the surf zone, particularly in crevices at low tide and below. Description: This species varies widely in sculpture. Eastern Australian shell usually has strong spiral sculpture; there are seven to nine strong spiral ribs on body whorl, with intervening grooves of about the same width, and ribs and grooves possess secondary spiral riblets. Anterior fasciole is about the same size as spiral ribs. Columella is smooth, and outer lip internally reflects external sculpture. Coloration of shell is

6-bromoisatin The chloroform extracts from the egg masses and hypobranchial glands of this species have been reported to inhibit the proliferation of a range of lymphoma and adherent cell lines from solid reproductive and colon tumors (Benkendorff et al., 2015). Anti-inflammatory activity: The chloroform extract of the hypobranchial gland of this species inhibited the production of NO with an EC50 value of 30.8 µg/mL; downregulated the production of TNFα in RAW264.7 (EC50:43 µg/mL; and downregulated the production of PGE2 in 3T3 fibroblasts (EC50:34.2 µg/mL) (Ahmad et al., 2018). Antimicrobial activity: The extracts of the egg mass of this species have shown activity against human pathogenic

88

Biology and Ecology of Pharmaceutical Marine Mollusks

bacteria, viz. S. aureus, E. coli, and P. aeruginosa. The activity profile of the different extracts/compounds is given below. Extract or Compound

Activity Profile

CHCl3

Inhibits Gram +ve and Gram −ve human pathogenic bacteria and C. albicans in the range of 0.1–1 mg/mL

Diethyl ether

Inhibits Gram +ve and Gram −ve human pathogens at 10 mg/mL Inhibits Gram +ve and Gram −ve human pathogens at 0.1 mg/mL Inhibits human pathogens at 0.5–1 mg/mL and C. albicans at 0.1 mg/mL Inhibits Gram +ve and Gram −ve human pathogenic bacteria in the range of 0.1–1 mg/mL; >1 mg/mL for C. albicans

EtOH Tyrindoleninone 6-Bromoisatin

Tyriverdin

Chicoreus ramosus (Linnaeus, 1758)

Inhibits human Gram +ve and Gram −ve pathogens at 0.0005 mg/mL; active against C. albicans at 0.001 mg/mL

Tyriverdin Source:  Benkendorff et al. (2015). Traditional medicines: The volatile and bioactive compounds extracted from the operculum of this species have been found to be useful in traditional medicines. The compound acetamide is a cosmetic ingredient for skin and hair; the phenolcontaining smoke is fragrant and is used as an antioxidant, oral anesthetic drug, and treatment for ingrown toenails; and the compound para cresol is an ingredient in fragrance and is useful as an antioxidant (Nongmaithem et al., 2017).

Order: Neogastropoda Family: Muricidae Common name: Ramose murex or branched murex Distribution: Indo-West Pacific: South Africa Mozambique, Tanzania, Madagascar, Red Sea, Gulf of Oman, Aldabra, Chagos, and Mauritius; eastern Polynesia, southern Japan, New Caledonia, and Queensland Ecology: It occurs on sandy and rubble bottoms near coral reefs, to depths of about 10 m. Description: This species has a large, solid, very rugged, and heavy shell of up to 330 mm in length. It has a relatively globose outline, possessing a short spire, a slightly inflated body whorl, and a moderately long siphonal canal. Conspicuous, leaflike, recurved hollow digitations are seen as ornamentation in the shell. It also presents three spinose axial varices per whorl, with two elongated nodes between them. Shell is colored white to light brown externally, with a white aperture, generally pink towards the inner edge, the outer lip, and the columella. Biology Food and feeding: As is the case in other Muricidae, this species is a carnivorous predatory species, usually feeding on bivalves and other small gastropods. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antibacterial activity: The organic extracts of this species showed antibacterial activity against human pathogenic bacteria, and the values of inhibition zone are given below. Inhibition of Zone (mm)

    

   

Acetamide    Phenol   Para cresol Nongmaithem et al. (2017) also reported that the compound murexine of the hypobranchial glands of this species exhibited muscle relaxing activities, and, along with adenosine, it has analgesic activity.

E. coli

S. typhi

S. paratyphi

K. pneumonia

S. aureus

2.6

7.2

8.5

5.4

2.8

Source:  Jayanthi et al. (2016).

Antifungal activity: The organic extracts of this species have shown antifungal activity against A. niger and Penicillium spp. with the inhibition zone values of 2.4 and 11.0 mm, respectively (Jayanthi et al., 2016).

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Marine Mollusks

Antimicrobial activity: The organic extracts of both the tissues and eggs of this species were found to inhibit the growth of pathogenic bacterial strains. The maximum zone of inhibition of 12 mm was observed against P. vulgaris in the crude ethanol extract followed by 8 mm against S. paratyphi at the concentration of 50 µL. Minimum inhibition zone of 2 mm was obtained by ethanol extract against Streptococcus mutans and by methanol extract against S. dysentriae (Giftson et al., 2015). Medicinal uses: The operculum of the shell of this species had traditional therapeutic uses in the treatment of skin diseases, wounds in the stomach, arthritis, eye and ear diseases, and uterus diseases (Ahmad et al., 2018).

Chicoreus virgineus (Röding, 1798) (=Murex virgineus)

days, and only a few juveniles measuring between 1.7 and1.9 mm emerged; the rest of the eggs functioned as “Nurse eggs” (Jagadis et al., 2013). Compound(s) and Activities Antibacterial activities: The crude extracts of this species showed antibacterial activity against human pathogenic bacteria, and the values of zone of inhibition ranged from 2 mm to 10 mm (Lenin, 2011). Medicinal uses: The operculum of the shell of this species had traditional therapeutic uses in the treatment of skin diseases, wounds in the stomach, arthritis, eye and ear diseases, and uterus diseases (Ahmad et al., 2018).

Chicoreus sp. Compound(s) and Activities Antiatherosclerotic activity: The methanolic crude extract of this unidentified species showed highest antiatherosclerotic activity at 25 µg/mL (Sarizan, 2013).

Tenguella marginalba (Blainville, 1832)

Order: Neogastropoda Family: Muricidae Common name: Virgin murex Distribution: From Red Sea to Bay of Bengal Ecology: It occurs in intertidal areas. Description: Shell of this species is moderately large in size and fusiform; spire is acute; body whorl is large and inflated; sculpture is composed of four rounded varices ornamented with six to seven strong spiral cords alternating with a few minor cords; inter spaces are ornamented with fine threads; shoulder is bearing a prominent spine; aperture is large and ovate; anal sulcus is not deep; outer lip is thick, and coarsely denticulate with a conspicuous tooth on the lower part; inner lip is slightly twisted at anterior region; siphonal canal is broad and distally curved upwards; color of the shell is pale brown with a slight pinkish band on middle of body whorl; aperture is white and margin of aperture is pinkish white. Adult shell size varies between 60 mm and 160 mm. Biology Food and feeding: As in C. ramosus. Reproduction: In the Gulf of Mannar (India), spontaneous breeding of this species was found to commence from June. Egg cases (40–140), which were released during October– December, were “vase” shaped and measured 1.5 cm in height. Number of eggs within the egg case was highly variable, ranging from 100 to 380. Eggs were spherical, embedded in jelly mass within the egg case. Development took nearly 20

Order: Neogastropoda Family: Muricidae Common name: Mulberry whelk Distribution: North and east coasts of Australia; islands in the central Indo-Pacific Ocean Ecology: It is common on rocks in the intertidal zone, where adults hide in cracks. It is also found in estuaries. Description: It has a strong, robust shell which can grow to about 35 mm. Each body whorl has five rows of purple or blackish, roughly square, nodules, separated by pale gray areas with fine sculptured vertical and horizontal lines. Lip is curved with four similar-sized ridges or teeth on its inner surface. Columella or central axis of the shell is white and is stout with a smooth surface. Interior of the shell is purplegray, contrasting with the cream teeth and lip. Biology Food and feeding: It is a carnivorous, predatory species, feeding on barnacles, mussels, and oysters by drilling a small circular hole in the shell. Reproduction: Not reported.

90

Compound(s) and Activities Antibacterial activity: The content of the egg mass of this species showed antibacterial activity by inhibiting human pathogenic bacteria, viz. Staphylococcus aureus, E. coli, and P. aeruginosa at 10 mg/mL (Benkendorff et al., 2015).

Concholepas concholepas (Bruguière, 1789)

Biology and Ecology of Pharmaceutical Marine Mollusks

showed a significant antitumor effect, with decreased tumor growth and incidence, prolonged survival, and lack of toxic effects. Analysis of serum from treated mice showed an increased interferon-gamma and low interleukin-4, confirming that these hemocyanins induce a T helper type 1 cytokine profile. Therefore, the hemocyanin of the above species may be an alternative candidate for providing safe and effective immunotherapy for human superficial bladder cancer (Moltedo et al., 2006).

Pleuroploca trapezium (Linnaeus, 1758)

Order: Neogastropoda Family: Muricidae Common name: Chilean abalone Distribution: Eastern Pacific and Western Atlantic: From Lobos de Afuera Island, Peru to Cape Horn, Chile Ecology: It lives on rocky substrates and in tidepools and rock crevices from the lower intertidal to a depth of 40 m. Description: It has a thick, slightly oval, and white-brown to purple-gray shell. Its very few whorls makes it resemble a Phrygian cap in shape. Outer surface of the shell shows strong lamellose ribs, which are both radial and circular-concentric. It attains a maximum length of 15 cm. Shell is made of calcite with an inner layer of aragonite. Shells of this species are used as ashtrays in Chile. Biology Food and feeding: It is a predator, feeding primarily on mussels, Semimytilus algosus and Perumytilus purpuratus; and barnacles, Chthamalus scabrosus. Reproduction: Egg masses of this species are composed of about 250 egg capsules, and each capsule contains 700– 1400 eggs. These capsules are found attached to substrate by a stalk. Larva emerges from the egg and remains in the water column for a long period of time before settling. Compound(s) and Activities Growth stimulating activity: A heparin-binding factor with mitogenic growth-stimulating activity in T3 fibroblasts has been isolated from this species. Mitogenic heparin binding can promote angiogenesis and increase the rate of dermal repair necessary for wound healing (Benkendorff et al., 2015). Anticancer/antitumor activity: The hemocyanin subunits (CCHA and CCHB) of this species have been reported to possess immunotherapeutic effects and are of potential use in the treatment of bladder and prostate carcinoma (Benkendorff et al., 2015). Mice treated with the hemocyanin of this species

Order: Neogastropoda Family: Fasciolariidae Common name: Trapezium horse conch Distribution: Indo-West Pacific: from East Africa, to Melanesia; north to Japan, and south to northern Queensland and New Caledonia; rare in Australia Ecology: It lives in the benthic zone on seagrass beds at depths between 0 and 40 m. Description: Golden brown shell of this species is solid and heavy. Its shell size varies between 85 mm and 250 mm, with a common length of 200 mm. Spire is of moderate length. Apex is usually eroded. Sutures are constricted. Shoulders on the whorls are covered with spiral rows of slightly pointed strong nodules. Surface is covered with fine, brown, incised spiral lines, mainly in pairs. Outer lip is dentate, with seven pairs of teeth situated where the paired lines meet the edge. Its oval aperture is pale with strong ridges internally. Columella is smooth posteriorly. Siphonal canal is extended and short. Fasciole is weak. It attains a maximum length of 28.0 cm. Biology Food and feeding: It is an active predator, preying on tube worms, vermetid, and other mollusks, including the spiny cerith (Cerithium echinatum). Reproduction: This species lays about 140 conical egg capsules at a time. Embryos of the egg capsules develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antioxidant activity: The body extract of this species exhibited the highest antioxidant activity in DPPH and SOS assays

91

Marine Mollusks

with EC50 of 0.93 and 0.95 mg/mL, respectively (Gopeechund et al., Sympo​sium.​wioms​a.org​/wp-c​onten​t/upl​oads/​2015/​10/A.​GOPE​ECHUN​D.pdf​). Anand et al. (2010) reported that the meat extracts of this species showed significant antioxidant activity range of 10.3%–50.3% at a concentration range of 810–4050 µg/mL. The meat of this species may therefore be popularized as an important seafood. Ponnusamy et al.(2016) reported that the methanolic extract of this species is a good scavenger of DPPH radical with an IC50 value of 4021 μg/ml.

Marmorofusus nicobaricus (Röding, 1798) (=Fusinus nicobaricus)

the highest activity against (3 mm) S. flexeneri and E. coli (3 mm) and the lowest against S. typhi (1 mm). Crude extract of chloroform exhibited the highest activity (4 mm) against S. flexneri. The crude extract of ethylacetate showed the maximum activity against P. fluorescens (8 mm), and very meager activity was exhibited against M. tuberculosis (1 mm). S. flexneri exhibited the uppermost activity (5 mm) in crude extract of methanol and chloroform (1:1). Of the 14 compounds identified and characterized, isothiocyanatocyclohexane, 2,4-Di-tert-butylphenol, 9,12-Octadecadienoic acid(Z,Z), 1,4- Benzenediamine N-(1,3-dimethylbutyl)-N’-ph enyl, 1-Hex​adeca​nol,2​-meth​yl,1,​2-Ben​zened​icarb​oxyli​c acid, 1- Docosanol, methoxyacetic acid,2-pentadecyl ester, and Ergost-5- en-3-ol,(3a) might be responsible for antibacterial activity (Janaki et al., 2015).

   

Isoth​iocya​natoc​ycloh​exane​  2,4-​Di-te​r t-bu​tylph​enol

Order: Neogastropoda Family: Fasciolariidae Common name: Nicobar spindle Distribution: Pacific Ocean along Japan, New South Wales, Australia, New Guinea, and Hawaii Ecology: This benthic species occurs from shallow subtidal waters to a depth of 40 m. Description: Shell of this species is moderately large, fusiform, and solid; spire is elevated with pointed apex; suture is constricted; shoulders are sculptured with compressed knobs; whorls are sharply angulate; sculpture is composed of strong spiral ridges and intercepting axial striae; siphonal canal is long; plications are absent on columella; aperture is ovate and lirate within; and outer lip is strongly crenulated. Color of the shell is white with reddish-brown flamelike markings extending all over the surface. Aperture is white. Shell size varies between 75 mm and 180 mm. Biology Food and feeding: It is believed to be a molluscivore, feeding on other mollusks. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antibacterial activity: The organic extracts of this species showed antibacterial activity against human bacterial pathogens. The crude methanol extract of this species showed

9,12-Octadecadienoic acid(Z,Z)

1,4-Benzenediamine N-(1,3-dimethylbutyl)-N’-ph enyl, 1-Hex​adeca​nol,2​-meth​yl,1,​2-Ben​zened​icarb​oxyli​c acid

 

   1-Docosanol   Methoxyacetic acid,2-pentadecyl ester

Ergost-5-en-3-ol,(3a)

92

Oxymeris maculata (Linnaeus, 1758) (=Terebra muculata)

Order: Neogastropoda Family: Terebridae Common name: Marlinspike auger, big auger Distribution: Indo-Pacific: From East Africa, Sudan, Yemen, India, Maldives, Andaman, and Nicobar Islands; Cocos (Keeling) and Christmas Islands to Pitcairn; north to Japan and Hawaii; south to Australia, including Socorro Island (Mexico) Ecology: It is found in coarse and fine sand in intertidal areas; occurs at the low tide mark; usually crawls under the sand surface with the foot buried deeply in the sand; depth range 0–210 m. It leaves characteristic wide tracks on sand when moving. Description: It has an elongated, thick, and heavy shell, which attains a maximum length of 27.5 cm. Its aperture is quadrate, with a medially angular inner lip. Shells feature tan and brown colors. Venoms of terebrid snails may offer an additional source of novel biologically active peptides. Biology Food and feeding: It is a predator, feeding mainly on enteropneust and polychate worms. It uses its venom to paralyze its prey. Predator: T. maculata is preyed upon by larger organisms such as fish, crabs, and gastropods such as Natica spp. and Murex spp. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antiatherosclerotic activity: This species has been reported to possess potential antiatherosclerotic substances (Sarizan, 2013). nAChRs inhibitory activity: The extracts of venom glands containing pharmacologically active peptides exhibited inhibitory activity on the neuronal nAChRs (Nicotinic acetylcholine receptors, which serve diverse and often critical functions throughout the central and peripheral nervous systems). The venoms of terebrid snails may therefore offer an additional source of novel biologically active peptides (Kendel et al., 2013).

Terebra argus (Hinds, 1844)

Order: Neogastropoda Family: Terebridae Common name: Hawaiian eyed auger, auger auger

Biology and Ecology of Pharmaceutical Marine Mollusks

Distribution: Central Pacific Ecology: It is moderately common, primarily in lagoons and pinnacle sand patches; low tidal on sand. Description: In this species, shells are designed for plowing through sand leaving a trail behind them. Color of the shell is ivory, usually with three rows of faint nebulous yellow spots per whorl. Outline of whorls is straight. Aperture is quadrate and columella is recurved. Shell reaches a maximum size of 10.8 cm. It has a venom apparatus which consists of a harpoonlike radular tooth, radular sac, venom duct, and venom bulb. Biology Food and feeding: Terebra species primarily feed on the enteropneust Ptychodera flava. Reproduction: The sexes are separate in terebrids, and fertilization is internal. Each egg mass contains several egg capsules. Eggs from these capsules develop into a trochophore stage, which is passed rapidly, and by the end of the 9th day, the embryos are elongate veligers with an extended head vesicle. Compound(s) and Activities nAChRs inhibitory activity: The extracts of venom glands of this species containing pharmacologically active peptides exhibited inhibitory activity on the neuronal nAChRs. The venoms of terebrid snails may therefore offer an additional source of novel biologically active peptides (Kendel et al., 2013).

Terebra consobrina (Deshayes, 1857)

Order: Neogastropoda Family: Terebridae Common name: Auger snail Distribution: Red Sea and Indian Ocean; along Madagascar and Mauritius Ecology: It lives on the upper slope and continental shelf soft bottom. Description: Shell of this species is heavy with coarse spiral sculpture. Subsutural band is rather flattened and wide, and band below the subsutural demarcation is not thickened. Size of an adult shell varies between 70 mm and 135 mm. It has a venom apparatus that is similar to that of Conus snails. Biology: Not reported. Compound(s) and Activities nAChRs inhibitory activity: The extracts of venom glands of this species containing pharmacologically active peptides exhibited inhibitory activity on the neuronal nAChRs. The venoms of terebrid snails may therefore offer an additional source of novel biologically active peptides (Kendel et al., 2013).

93

Marine Mollusks

Melo melo (Lightfoot, 1786) (=Cymbium melo)

minimum activities (inhibition zone,11 mm) with A. flavus (Datta et al., 2015; Kanagasabapathy et al., 2011).

Cymbiola vespertilo (Linnaeus, 1758)

Order: Neogastropoda Family: Volutidae Common name: Indian volute, bailer shell, bailer volute, beggar’s bowl Distribution: Restricted to Southeast Asia: from Burma, Thailand, and Malaysia to the South China Sea and the Philippines Ecology: It usually dwells in muddy bottoms (near mangroves and seagrasses) of littoral and shallow sublittoral zones at a maximum depth of nearly 20 m. Description: The notably large shell of M. melo has a bulbous or nearly oval outline, with a smooth outer surface presenting distinguishable growth lines. Outside of shell color is commonly pale orange, sometimes presenting irregular banding of brown spots, while the interior is glossy cream, becoming light yellow near its margin. Columella has three or four long and easily distinguishable columellar folds. It has a wide aperture, nearly as long as the shell itself, but there is no operculum. Shell’s spire is completely enclosed by the body whorl, which is inflated and quite large and has a rounded shoulder with no spines. Apex is of smooth type. Fleshy body is brown with white stripes, and its large foot is plain and pale on the underside. It has a pair of slender tentacles, a long siphon that sticks out of the notch at the front of the shell, and a long proboscis, both banded brown and white. This volute is known to produce pearls; however, the M. melo pearl has no nacre, unlike the pearl of a pearl oyster. Maximum shell length of this species is up to 275 mm. Biology Food and feeding: It is a carnivore and specialized predator of other continental shelf predatory gastropods, notably Hemifusus tuba and Babylonia lutosa. It is also a known predator of the dog conch, Strombus canarium. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antimicrobial activities: The organic extracts of this species containing peptides and amide groups showed antimicrobial activity. The mucus extract of this species showed maximum zone (24 mm) of inhibition against K. pneumoniae, and the body tissue extract displayed minimum zone (11 mm) of inhibition in S. typhi. Maximum antifungal activity (inhibition zone 14 mm) was against Trichophyton mentagarophytes and

Order: Neogastropoda Family: Volutidae Common name: Bat volute Distribution: Central Indo-Pacific: off the Philippines and Northern Australia Ecology: It is a benthic species; depth range 0–20 m. Description: Shell of this species is armed with spinous tubercles, sometimes smooth but never ribbed; spiral whorls gradually diminish in size but are not distorted; apex is thick and obtuse; pillar has four plaits. Size of an adult shell varies between 45 mm and 160 mm. Biology Food and feeding: These are predatory sea snails. They are amazingly fast when feeding on other mollusks. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Left-handed C. vespertilio shells are common. Compound(s) and Activities Antibiotics: The symbiotic bacteria associated with this species have been reported to inhibit the growth of pathogenic bacteria. It is suggested that this species may be the best candidates for the development of a new antibiotic (Pringgenies, 2010).

Kelletia kelletii (Forbes, 1850) (=Fusus kelletii)

Order: Neogastropoda Family: Buccinidae Common name: Kellet’s whelk

94

Biology and Ecology of Pharmaceutical Marine Mollusks

Distribution: From Isla Asunción, Baja California, Mexico to Monterey, southern California, the United States Ecology: It lives in subtidal kelp forests, rocky reefs, and cobble-sand interfaces at depths ranging from 2 to 70 m. Description: It is the largest buccinid gastropod, with a robust, spindle-shaped, spiraled shell. Shells are white to tan and are often covered with encrusting organisms such as bryozoans, sponges, and algae. Shell attains a maximum size of 17.5 cm. Biology Food and feeding: Kellet’s whelks are opportunistic carnivores that feed on dead or dying organisms, often forming feeding aggregations. They will also actively pursue prey, including several species of turban snails. Ingestion occurs through the scraping of the radula and the muscular suction action of the prehensile proboscis, a tubular extension used for feeding, which can be extended up to three times the length of the shell. They are voracious eaters and often feed on crustaceans also. Predators: Predators of this species include the moon snail, giant seastar, octopus, and sea otter. Juvenile Kellet’s whelks are also eaten by a variety of fish. Reproduction: In California, Kellet’s whelks display sexual dimorphism, with females being the larger individual in a mating pair. Females are generally sexually mature between 6.5 and 7.0 cm, with males maturing at slightly smaller sizes. Fertilization is internal, and spawning occurs annually in March, April, and May, with aggregations of 15–20 mating pairs commonly seen during spawning. Oval-shaped egg capsules are deposited in clusters on hard substrate, including reef, discarded mollusk shells, or other Kellet’s whelks. Egg deposition may occur over several days at several locations, or all within one day. Egg capsules generally contain between 400 and 1,200 eggs but may contain up to 2,200 eggs. Embryos begin development within the capsule and emerge into the water column as free-swimming veliger larvae. Veliger size is inversely related to egg capsule size, with smaller capsules containing larger veligers. The length of time in the planktonic larval stage is unknown (Anon., https:// en.wikipedia.org/wiki/Kelletia_kelletii). Compound(s) and Activities Antibacterial and anticancer activities: Kelletinin I and II isolated from this species inhibited the growth of B. subtilis and L1 leukemia cells as antibacterial and anticancer agents (Datta et al., 2015). Further, these two compounds displayed in-vitro growth inhibitory effects, with GI50 values of ∼0.07 μM in murine L1210 leukemia cells (Ciavatta et al., 2017).

            Kelletin I            Kelletin II

Buccinum undatum (Linnaeus, 1758)

Order: Neogastropoda Family: Buccinidae Common name: Common whelk, waved buccinum Distribution: Northern Atlantic: United Kingdom, Ireland, France, Norway, Iceland, various other northwest European countries, some Arctic islands, and North America as far south as New Jersey Ecology: This subtidal species normally inhabits soft bottoms in the sublittoral zone and occasionally on the littoral fringe, where it is sometimes found alive at low tide. It does not adapt well to life in the intertidal zone due to its intolerance for low salinities. If exposed to air, it may crawl from its shell, risking desiccation. Description: Shell of this species is solid, ovate-conical, and ventricose (a spiral shell having the body whorls rounded or swollen in the middle). Spire contains seven or eight whorls. These are convex and crossed by oblique folds, which are thick and waved. Shell surface has a sculpture of vertical, wavy folds (hence the name undatum, which means wavy). Wavy folds are crossed by numerous incised, very prominent spiral lines, some of which are paired. The white and very large aperture of the shell is broadly oval and tapers to a deeply notched siphonal canal. Outer lip is arched. Color of the shell is very pale, white, yellowish, or reddish. In life, shell is covered in a bright, yellowish-brown periostracum. Maximum height of the shell is 10 cm and maximum width is 6 cm. This animal emits a thin and copious slime. Biology Food and feeding: It is an active predator on polychaetes, bivalves, and urchins. It is also a carrion (dead and rotting flesh) feeder. These animals frequently approach seastars that are extracting bivalves from sediment bottoms and may benefit by feeding on prey remains left by seastars or by foraging in sediments recently disturbed by seastars. The proportion of whelks with food in their stomachs varies seasonally and with habitat, being greatest on sandy bottoms (Himmelman and Hamel, 1993). Reproduction: In this species (for European populations), gonad maturation takes place during the spring and summer, whereas egg laying occurs during the winter. Fertilization is internal, and eggs are contained within capsules laid on hard

95

Marine Mollusks

benthic substrates. Development takes place inside the egg capsules, and hatching of juveniles occurs after 3–8 months.

Harpa major (Röding, 1798) (=Harpa conoidalis)

Compound(s) and Activities Antibacterial activity: The acidic extracts of this species showed growth inhibition diameter of less than 7 mm against M. luteus and more than 10 mm against Listonella anguillarum (Defer et al., 2009). Antiviral activity: This species showed 60.7% inhibition of viral activity at a protein concentration of 130 µg/mL (Defer et al., 2009).

Buccinum sp.

Order: Neogastropoda Family: Buccinidae Common name: True whelk Distribution: English Channel and North Sea Ecology: These whelks live on rocks, where they occur in large numbers. Description: Shell of this unidentified species is ovate or ovateconical and elongated. Spire is moderate and pointed. Aperture is oval or oblong with a deep notch anteriorly and without a siphonal canal. Columella is plain and is not flattened. There sometimes exists a fold at the base of the columella. Outer lip is plain, quite thin, sometimes recurved, and forming a margin on the exterior. Thin, horny operculum is ovate and concentrically striate. Biology Food and feeding: These whelks are carnivores and scavengers, feeding on dead or damaged marine animals. Reproduction: Sexual maturity in Buccinum sp. has been reported to occur after 5 to 7 years depending on the sex of the individual and other factors. In the North Sea whelks reproduce in the autumn. The spawning period may be different in other areas. Females retreat to hard substrate areas to deposit their egg capsules. Often several females will attach their eggs to the same egg mass. The eggs hatch in winter into benthic juvenile snails. Whelks have a fairly long life span of at least 10 years. Antiatherosclerotic activity: It is reported that 2 hours after a single dietary load of this unidentified species, the patient’s blood serum acquired marked antiatherosclerotic properties. Further, incubation of this serum with cultured atherosclerotic cells led to a fall in intracellular cholesterol retention (Orekhov, 2013).

Order: Neogastropoda Family: Harpidae Common name: large harp, major harp Distribution: Off East Africa, Tanzania, Mozambique, Mascarene Basin; off Hawaii Ecology: It lives in shallow waters near coral reefs; lower intertidal fringe and sublittoral to shelf zones; depth range 62–64 m. Description: Shell of this species is medium to large in size; it has an ovate body with a heavily calloused spire; body whorl is inflated; aperture is large and widely ovate; outer lip is arcuate; body whorl is ornamented with 12 axial ribs ending in spines on subsutural ramp; and interspaces are provided with fine axial striae. It has a base shell color of a deep pinkishrose or reddish-tan, overlaid with white zig-zag flammules. Ribs are a deep rose-tan overlaid with thin white stripes and dark brown lines. Size of the shell varies between 60 mm and 130 mm. Biology Food and feeding: It is a predatory sea snail, feeding primarily on small crabs. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antioxidant activity: The crude methanolic extracts of this species showed antioxidant activity (Pachaiyappan et al., 2014). Antimicrobial activity: The human bacterial pathogen S. paratyphi was found to show maximum susceptibility (9.2 mm inhibition zone) against the ethanol extracts of Harpa major. On the other hand, the fungal pathogen A. niger showed maximum susceptibility (4.0 mm inhibition zone) against ethanol extracts of this species (Suresh et al., 2012). Anticoagulant activity: The GAGs isolated from this species showed anticoagulant activity. The purified sample showed 1.4 and 2.3 folds in activated partial thromboplastin time and thrombin time (TT) assays, respectively (Mohan et al., 2016).

96

Biology and Ecology of Pharmaceutical Marine Mollusks

Babylonia japonica (Reeve, 1842)

Order: Neogastropoda Family: Babyloniidae Common name: Japanese Babylon, Japanese ivory shell Distribution: Indo-Pacific; North to the Southern shores of Japan; off Korea and Taiwan Ecology: It inhabits littoral and shallow sublittoral zones; prefers shallow sandy or muddy sea water. Description: Shell of this species is somewhat thick with a high spire. Shell has a cream color with brown spots and blotches. Whorl has two bands of dots spiraling around the shell body. Length of the shell varies between 40 mm and 85 mm. Compound(s) and Activities Antinicotinic activity: The surugatoxin and neosurugatoxin of this species have been reported to possess antinicotinic activity. The antinicotinic activity of the latter compound is found to be 100 times that of the former (Datta et al., 2015). Others: The surugatoxin (50 nmol/kg i.v.) of this species has been reported to produce a prolonged fall of blood pressure in anaesthetized cats. This hypotensive effect was neither blocked by atropine and propranolol nor by spinal cord transaction (Hayashi, 1975).

Babylonia spirata (Linnaeus, 1758)

Order: Neogastropoda

Common name: Spiral babylonia snail. spiral Babylon Distribution: Indo-West Pacific Ecology: It inhabits mud, sand, and shell substrates at a depth range of 0–60 m. Description: Shell of this species is large, up to 70 mm in height, and is smooth and heavy; body whorl is inflated; spire is high and elongate; and sutures are deep and channeled. Shoulders are prominent; whorls are inflated; columella is smooth and is heavily calloused; umbilicus is broad, deep, and heavily calloused. Anterior canal is in the form of oblique notch at the base of aperture; and posterior canal is well developed. Aperture is large and ovate, outer lip is sharp and strongly flexed at the top, and interior of aperture is smooth and thickened. Color of shell is white with prominent light-brown blotches, oblique streaks, and spots. Aperture, outer lip, and columellar callus are white; tip of apex and aperture are tinged blackish; and fresh shells are covered by light-brown periostracum. It is a commercial species. Biology Behavior: It is often half buried in the ground, emerging as the tide starts to come in. Food and feeding: It is carnivorous, feeding on various food organisms like shrimps, crabs, and oysters. Reproduction: It has a rapid growth rate, early maturity, and continuous breeding behavior. It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antioxidant activity: The crude methanol extract of this species has shown antioxidant activity. The values of the total antioxidant activity and percentage of inhibition in the 1.1-diphenyl-2-picrylhydrazyl scavenging activity were found to be 510 µg/mg and 76.7%, respectively (Jayanthi et al., 2016; Pachaiyappan et al., 2014). Antibacterial activity: The organic extracts of this species showed antibacterial activity against human pathogenic bacteria, and the values of inhibition zone are given below.

Family: Babyloniidae Inhibition of Zone (mm)

E. coli

S. typhi

S. paratyphi

A. hydrophila

V. cholerae

V. parahaemolyticus

K. pneumoniae

S. aureus

3.2

2.9

3.9

12.4

2.9

4.1

4.4

2.6

Source:  Jayanthi et al. (2016).

Antifungal activity: The organic extracts of this species have shown antifungal activity against A. niger and Fusarium spp. with the inhibition zone values of 8.0 and 18.0 mm, respectively (Jayanthi et al., 2016).

Periyasamy et al. (2012) reported that the crude ethanol extract of this species showed the maximum inhibition zone (12 mm) with P. aeruginosa, and the minimum inhibition zone (2 mm) was with Staphylococcus aureus. On the other

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Marine Mollusks

hand, the water extract showed the highest activity against V. parahaemolyticus, Staphylococcus aureus, and C. albicans. Anticoagulant activity: The crude extract of this species showed anticoagulant activity (134 USP units/mg) (Periyasamy et al., 2013).

Babylonia zeylanica (Bruguière, 1789)

than in Babylonia spirata; sutures are not canaliculated; and spire is high, ending in a dark purple apex. Aperture is dark; outer lip is sharp and smooth, but not flexed at top; columella is smooth with heavy broad callus posteriorly but narrow anteriorly; and a strong parietal ridge is seen very close to the outer lip. Umbilicus is broadly open with a row of teeth on the outer margin, fasciole has a ridge on the inner edge, anterior canal is broad and deep, and posterior canal is not distinct. Color of the shell is white with large brown blotches. The meat and operculum of this species are commercially important. Biology Food and feeding: It is carnivorous, feeding on various food organisms like shrimps, crabs, and oysters. Reproduction: It has a rapid growth rate, early maturity, and continuous breeding behavior. It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults.

Order: Neogastropoda Family: Babyloniidae Common name: Indian Babylon Distribution: Western Indian Ocean: India Ecology: This benthic, coastal species inhabits sandy areas. Biology: Shell of this species is large, up to 70 mm in height; fusiform, and with less inflated whorls; body whorl is narrower

Compound(s) and Activities Antioxidant activity: The methanolic extract of this species exhibited total antioxidant activity (78.6 at 10 mg/mL) (Velayutham et al., 2014). Antibacterial activity: The organic extracts of this species showed antibacterial activity against human pathogenic bacteria, and the values of inhibition zone are given below.

Inhibition of Zone (mm) E. coli

S. typhi

S. paratyphi

A. hydrophila

V. cholera

V. parahaemolyticus

S. aureus

4.9

2.7

2.9

2.8

3.5

4.8

4.7

Source:  Jayanthi et al. (2016).

Antifungal activity: The organic extracts of this species have shown antifungal activity against A. niger and Fusarium spp., with inhibition zone values of 1.9 mm and 7.0 mm, respectively (Jayanthi et al., 2016). Antimicrobial activity: The human bacterial pathogen K. pneumoniae was found to show maximum susceptibility (10.1 mm inhibition zone) against the ethanol extracts of this species. On the other hand, the fungal pathogen C. albicans showed maximum susceptibility (7.1 mm inhibition zone) against methanol extracts of this species (Suresh et al., 2012). Kanchana et al. (2014) reported that the organic extract of this species showed significant antifungal activity against A. fumigatus with the highest zone of inhibition (18 mm). Anti-inflammatory activity: The benzene:methanol extract of this species showed anti-inflammatory activity. Wistar albino rats that received orally 100 or 200 mg/kg of the extract showed considerable reduction of paw edema. Further, this species also reduced the pain in analgesic activity at the extract concentration of 200 mg/kg (Ahmad et al., 2018).

Conus betulinus (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Betuline cone, beech cone Distribution: Indo-Pacific. Ecology: This benthic species dwells on sand flats, especially in shallow sublittoral zones, sheltered areas, and near seagrasses; depth range 0–20 m.

98

Description: Color of the shell is yellow or orange-brown, with revolving series of spots and short lines of chocolate brown upon narrow white bands. Spire is radiated with chocolate brown. Base of the shell is strongly grooved. Shell attains a maximum length of 17.5 cm. Almost all the species of Conus are venomous and are capable of “stinging” humans; therefore, live ones should be handled carefully or not at all. Biology Food and feeding of Conus spp.: These snails are predatory and prey on small fish (piscivore), other small mollusks (molluscivore), or polychaetes and hemichordates (vermivore). Reproduction of Conus spp.: The Conus species are broadcast spawners. Embryos develop into planktonic trocophore larvae and later into juvenile veligers.

Biology and Ecology of Pharmaceutical Marine Mollusks

Description: It has a thin shell which is inflated and grooved below. Color of the shell is white, clouded with orange-red and chestnut, forming two ill-defined bands, with indistinct revolving rows of white and chestnut articulations. Aperture is pink. Size of an adult shell varies between 42 mm and 82 mm. Compound(s) and Activities Treatment of Parkinson’s disease: The venom component of this species, viz. alpha-conotoxin BuIA, is a small peptide antagonist of nicotinic receptors that has become the standard pharmacological tool for differentiating nicotinic receptor subunits b2 and b4. These receptors are of considerable interest in Parkinson’s disease (Satheesh Kumar et al., 2015). The other venom component of this species is µ-conotoxin BuIIIC, although the pharmacological role of this component is as yet unknown.

Compound(s) and Activities Antibacterial activity: The methanol extract of this species showed antibacterial activity against Staphylococcus aureus with an inhibition zone of more than 10 mm (Kanchana et al., 2014). Periyasamy et al. (2012) reported that the tissue extracts of this species showed maximum zone of inhibition (15 mm) against Salmonella pullorum and minimum activity (4 mm) was observed in S. typhimurium. Anticancer activity: The venom of this species exhibited significant anticancer activity against HeLa cell lines (Sadhasivam et al., 2014).

Conus catus (Hwass in Bruguière, 1792)

Conus bullatus (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Cat cone Distribution: Occurs in the Red Sea, the Indian Ocean off the Aldabra Atoll, Chagos, Madagascar, Mauritius, Tanzania, and KwaZuluNatal; in the tropical Indo-West Pacific Region (Papua New Guinea, Marquesas, New Caledonia); off Australia (New South Wales, the Northern Territory, Queensland, and Western Australia) Ecology: It dwells intertidally to depths of 8 m; on rocky shores, reef flats, crevices, sand with or without vegetation, limestone, algal turf, and coral rubble. Description: Shell of this species is bulbous, with a convex, striate spire. Body whorl is striate, the striae rounded, usually obsolete above, granular below, olive, chestnut-, chocolate- or pink-brown, variously marbled and flecked with white, and often faintly white-banded below the middle. Size of an adult shell varies between 24 mm and 52 mm.

Order: Neogastropoda Family: Conidae Common name: Bubble cone Distribution: This species occurs in the Indian Ocean off the Mascarene Basin and Mauritius; in the Indo-West Pacific (the Philippines, New Caledonia) Ecology: It occurs in intertidal habitats on coral rubble, coral, muddy sand, and gravel, down to depths of 240 m; most commonly found at depths of 50 m.

Compound(s) and Activities Analgesic activity: The venom component of this species, viz. conopeptides, have been reported to possess analgesic activity (Kumar et al., 2015).

99

Marine Mollusks

Conus consors (Sowerby I, 1833)

Compound(s) and Activities As a pain killer: The conopeptide Contulakin-G (CGX1160) of the venom component of this species has been reported to produce significant analgesia in animals. It is also a pain killer and is in Phase I (clinical application). Antiepileptic activity: The compound conantokin-G (CGX1007) isolated from this species has antiepileptic properties (Phase 1). Further, this “sleeper peptide” could serve as a neuroprotective agent with potential applications in Alzheimer’s disease (Kumar et al., 2015).

Order: Neogastropoda Family: Conidae Common name: Singed cone Distribution: Indo-West Pacific: Marshall Islands, in Melanesia and off Queensland, Australia Ecology: It occurs at depths from 2 to 280 m in sand and silt. Description: Its depressed spire is conical, with a shallow channel and revolving striae, sometimes tessellated with chestnut. Body whorl is rather narrow, somewhat convex, grooved towards the base, somewhat round-shouldered, and rather thin. Color of the shell is white, yellowish, and orangebrown, variously clouded and indistinctly banded. Aperture is white. Size of an adult shell varies between 33 mm and 118 mm. It is piscivorous in its diet.

Conus gloriamaris (Chemnitz, 1777)

Compound(s) and Activities Pain killers: The conopeptide µ-conotoxins (or μ-conopeptides) of this species have several therapeutic applications as pain killers (Kumar et al., 2015).

Conus geographus (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Glory of the sea cone Distribution: Pacific and Indian Oceans: off the Solomon Islands; Philippines, and eastern Indonesia; New Guinea, and Samoa and Fiji Ecology: It occurs on sand and mud between 5 and 300 m deep. Description: It has a relatively large, slender shell with a tall spire. It is finely reticulated, with orange-brown lines enclosing triangular spaces similar to other textile cones, and two or three bands of chestnut hieroglyphic markings across its body. Tan coloration of the shell can vary from a lighter, golden color to a deeper dark brown, with intricate detailing. Shell can reach 16 cm in length. Compound(s) and Activities The venom component of this species is delta-conotoxin GmVIA, which has potential therapeutic applications (Shon et al., 1994).

Order: Neogastropoda Family: Conidae Common name: Geography cone, geographer cone Distribution: Red Sea, in the Indian Ocean off Chagos, Réunion, Madagascar, Mauritius, Mozambique, and Tanzania. Indigenous to the reefs of the Indo-Pacific region, except for Hawaii[4], and off Australia (the Northern Territory, Queensland, Western Australia) Ecology: It dwells in the sediment of shallow reefs. Description: It has a broad, thin shell which is cylindrically inflated. Ground color of the shell is pink or violaceous white, occasionally reddish. It has a mottled appearance, clouded and coarsely reticulated with chestnut or chocolate brown, usually forming two very irregular bands. Size of an adult shell varies between 43 mm and 166 mm.

Conus inscriptus (Reeve, 1843)

Order: Neogastropoda

Family: Conidae

100

Common name: Engraved cone, tiled cone Distribution: Red Sea and in the Indian Ocean off Madagascar and KwaZulu-Natal, South Africa; also found off Western Thailand and in the Aegean Sea Ecology: It is a benthic, subtidal species common in continental shelf areas. Description: Shell of this species is small, thin, and lightweight; spire is elevated; and apex is pointed. Body whorl is white and is ornamented with brownish yellow blotches, crescent-shaped tan markings are present on the apex, and its sides are convex. Aperture is white. Edge of outer lip is sharp. Periostracum is brown, smooth, thin, and translucent. Operculum is horny and calcareous. Shell color is ash-white, with dark chestnut hieroglyphic characters, interrupted by revolving series of spots in the middle and at the base. Size of an adult shell varies between 32 mm and 65 mm. Compound(s) and Activities Analgesic activity: The venom of this species exhibited potential analgesic activity, implying its importance in analgesic drug design research (Nayak, 2011). Antibacterial activity: The tissue extract of this species showed antibacterial activity. The maximum zone of inhibition (12 mm) was against Salmonella enteritidis, and minimum activity (3 mm) was observed in S. pullorum (Periyasamy et al., 2012).

Conus kinoshitai (Kuroda, 1956)

Order: Neogastropoda Family: Conidae Common name: Kinoshita’s cone Distribution: South China Sea and in the Pacific Ocean from the Philippines to the Solomons; also in the Indian Ocean from Mozambique, Madagascar, and Réunion Ecology: It is found in sandy and muddy habitats; depth range 100–400 m. Description: Size of an adult shell varies between 40 mm and 94 mm. Compound(s) and Activities Analgesic activity: The venom component of this species is µ-conotoxin KIIIA, which is a potent analgesic following systemic administration in mice (Khoo et al., 2009).

Biology and Ecology of Pharmaceutical Marine Mollusks

Conus magus (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Magical cone, magus cone Distribution: Western Central Atlantic and Western Pacific; Red Sea and in the Indian Ocean off Madagascar and the Mascarene Basin; also in Pacific Ocean from Indonesia to Japan and to the Marshall Islands, Wallis and Futuna, and Fiji Ecology: Found also in shallow subtidal (Ref. 3204), up to possibly 100 m for juveniles (Ref. 98471). It inhabits sandy coral reefs and shallow bays, hiding underneath rocks and dead corals; also in shallow subtidal areas; depth range 1–3 m. Description: This common species is very variable in pattern and shade of coloring. Its moderate spire is striate. Body whorl is long and rather cylindrical, closely striate below. Color of the shell is white, clouded with bluish ash, orange-brown, chestnut, or chocolate, everywhere encircled by narrow chocolate interrupted lines, often separated into somewhat distant dots. Middle of the body whorl is usually irregularly fasciate with white. The spire is tessellated with chestnut or chocolate. Size of an adult shell varies between 16 mm and 94 mm. Compound(s) and Activities Analgesic activity: The compound ziconotide (also known as SNX-111), which is a 25 amino acid peptide with three disulphide bonds, is present in the venom of this species. It possesses remarkable analgesic activity, which has proved to be 1,000 times more active than morphine in animal models of nociceptic pain (Suarez-Jimenez et al., 2012). Ziconotide has also been tested for neuro-protection as its efficacy has been tested against ischemic stroke and in coronary bypass surgery (Kumar et al., 2015). This compound has been licensed by Elan Pharmaceuticals under the name Prialt and is used for intratracheal treatment for chronic pain (Datta et al., 2015). Two peptide toxins, viz. omega-conotoxins MVIIA and MVIIB, have been isolated from the venom of this species. These toxins could serve as experimental tools and therapeutics in pain management.

101

Marine Mollusks

Conus marmoreus (Linnaeus, 1758)

Biology Shell of this species is moderately large. Spire is of low to moderate height. Ground colour is white; and last whorl is with a variably broad dark brown spiral band above centre. Aperture is translucent and is even in large specimens. Shell reaches a maximum length of 130 mm.

Order: Neogastropoda Family: Conidae Common name: Marbled cone Distribution: Indian Ocean; off Chagos and Madagascar; Bay of Bengal off India; western part of the Pacific Ocean to Fiji and the Marshall Islands; off Australia Ecology: It dwells on coral reef platforms and lagoon pinnacles, on coral debris, and in sand, often under rocks or among weed; depth range 1–30 m.

Compound(s) and Activities Conotoxin: This species contains O-Superfamily conotoxins, which may be of great use in drug development (Luo et al., 2007). Antibiotics: The bacterial symbionts of this species have yielded compounds such as acetic acid, propanoic acid, isovaleric acid, isobutyric acid, methylbutanoic acid, phthalic acid which serve as potentially new antibiotics (Hasanah et al., 2012).

Conus planorbis (Born, 1778)

Biology Its flattish spire is nodular. Outer lip flares towards posterior. Its distinctive, reticulated color pattern can range from black with white dots to orange with white reticulations, so arranged as to expose the white in rounded triangular large spots. Aperture is white or light pink. Size of an adult shell can vary between 30 mm and 150 mm. Compound(s) and Activities Antinociceptive activity: The peptide mr10a isolated from the venom of this species displayed potent antinociceptive activity (Layer, http:​//www​.jbc.​org/c​onten​t /ear​ly/20​00/07​/18/ j​bc.M0​03619​200.f​ull.p​df). Pain killer: The conopeptide χ-conotoxin MrIA/B isolated from the venom of this species could be used for the treatment of neuropathic pain (Kumar et al., 2015).

Conus miles (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Planorbis cone, ringed cone Distribution: Indo-West Pacific; Red Sea, in the Indian Ocean off Madagascar, the Seychelles, and the Mascarene Islands; in the Indo-West Pacific and Oceania; off Australia (Northern Territory, Queensland and Western Australia) Ecology: It is found in lagoons, among Halimeda spp. algal patches, and beneath dead coral on reef rock. Description: Whorls of the spire of the shell are striate, maculate with chestnut. Body whorl shows beaded striae below. Sometimes the granular striae cover the entire surface. Shell is orange-brown or chestnut, frequently light-banded in the middle and sometimes at the shoulder also. Its base is darker colored. Size of the shell varies between 26.1 mm and 82 mm. Compound(s) and Activities Conotoxin: This species contains J-conotoxin, pl14a; and toxins of P and T-Supefamiles with potential therapeutic applications (Jin et al., 2015).

Conus purpurascens (Sowerby I, 1833) Order: Neogastropoda Family: Conidae Common name: Soldier cone Distribution: Aldabra, Chagos, Madagascar, Mascarene Basin, Mauritius, Mozambique, the Red Sea, and Tanzania; and in the entire Indo-Pacific; off Australia (Northern Territory, Queensland, Western Australia) Ecology: It is known to live from immediate subtidal to a depth of 20 m on reefs.

Order: Neogastropoda

Family: Conidae

102

Common name: Purple cone Distribution: Central Pacific; off the Galapagos Islands and in the Gulf of California, Mexico Ecology: It is found between low tide and 40 m under rocks on sandy mud substrate. Description: Shell of this species is broad-shouldered, with a rude, striate spire. It is striate below, and the string is sometimes slightly granular. Shell is clouded with white or violet and brown or olive, with close lines of chestnut and minute white articulations. Sometimes it is irregularly white-banded in the middle. Size of the shell varies between 33 mm and 80 mm. Compound(s) and Activities Kappa conotoxin: The conopeptides (Conantokin-P) of the venom of this species serve as pain killers and are also are useful for other clinical indications. The conopeptide k-PVIIA (CGX-1051) of this species has shown a cardioprotective effect (preclinical phase) of CGX-1051 in a rat and dog model of myocardial ischemia/reperfusion (Kumar et al., 2015).

Conus radiatus (Gmelin, 1791)

Biology and Ecology of Pharmaceutical Marine Mollusks

Conus stercusmuscarum (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Fly-specked cone, fly-spotted cone Distribution: Western Pacific Ocean: Fiji, Marshall Islands, Papua New Guinea, Solomon Islands; also off Indonesia, Japan, Taiwan, the Philippines, and Australia (Northern Territory, Queensland) Ecology: It is found in intertidal and shallow subtidal zones to 25 m; in sand and beneath coral. Biology Size of the shell of this species varies between 27 mm and 64 mm. It is piscivorous.

Order: Neogastropoda Family: Conidae Common name: Rayed cone Distribution: Indo-West Pacific; off the Philippines, New Guinea, and Fiji Ecology: It inhabits sandy bottoms of continental shelf; depth range 10–150 m. Description: Color of the shell is pale yellowish to pale chestnut, often longitudinally indistinctly marked with deeper coloring. Spire is striate. Lower part of body whorl is distantly sulcate. Its white variety is frequently covered by a smooth olivaceous epidermis. Size of the shell varies between 30 mm and 109 mm. Compound(s) and Activities Conotoxin: Two potassium channel blockers, viz. kM conotoxin RIIIJ and kM RIIIK, with cardioprotective effects have been isolated from the venom of this species (Pati et al., 2015). Other derivatives of the venom of this species are conantokin-C (Wikipedia); Iota-conotoxin-like r11c (Anon., http://www.uniprot.org/uniprot/Q7Z096); and conophysin-R (Anon., http://www.uniprot.org/uniprot/P58990), the activities of which are yet to be known in detail.

Compound(s) and Activities Conotoxin: The conopeptide μ-conotoxin SmIIIA of the venom of this species has potential therapeutic applications as a pain killers and is also useful for other clinical indications (Kumar et al., 2015; Anon., http://www.uniprot.org/uniprot/ P60207). Another derivative of the venom of this species is delta-conotoxin-like SmVIA (Anon., http://www.uniprot.org/ uniprot/P69757), the activity of which is yet to be known in detail.

Conus striatus (Linnaeus, 1758)

Order: Neogastropoda Family: Conidae Common name: Striated cone Distribution: Indo-Pacific: Red Sea, Madagascar, Mascarene Basin, Mauritius, and Tanzania; off the Philippines, Australia (Northern Territory, Queensland, Western Australia), New Zealand, New Caledonia, and Thailand; also in Hawaiian islands Ecology: It is found in shallow subtidal areas; depth range 1–25 m.

103

Marine Mollusks

Description: It has a large, slim shell, the size of which varies between 44 mm and 129 mm. Shell is irregularly clouded with pink-white and chestnut or chocolate, with fine close-revolving striae, forming the darker ground color by close colored lines. Pointed spire is tessellated with chestnut or chocolate and white. Its shoulders are rounded and its sutures deep. Whorls are slightly channeled, carinate, and striate. Outer lip shows a pronounced posterior flare. Compound(s) and Activities Conotoxin: The bioactive compound striatoxin, a cardiotonic glycoprotein isolated from the venom of this species, was reported to have long-lasting isotropic action on guinea-pig left atria (Datta et al., 2015). Analgesic activity: SO‐3 (ω‐conotoxin), a new O‐superfamily conopeptide derived from the venom of this species, has been reported to target N‐type voltage‐sensitive calcium channels. Considering the significance of N‐type calcium channels for pain transduction, SO‐3 may have therapeutic potential as a novel analgesic agent (Wen et al., 2005). Neuroprotective activity: Two novel peptides (TTXresistant sodium channel blockers), viz. μ-conotoxins SIIIA and KIIIA, isolated from the venom of this species inhibit TTX-resistant sodium currents in neurons of frog sympathetic and dorsal root ganglia (Bulaj et al., 2005).

Conus ventricosus (Gmelin, 1791)

Order: Neogastropoda Family: Conidae Common name: Mediterranean cone Distribution: Mediterranean Sea Ecology: It is found in shallow waters in many differing habitats including mud, sand, seagrass, and rocks between 0.5 and 5 m depth. Description: Shell of this species is yellowish brown, pinkbrown, or olivaceous. It is sometimes chocolate-brown, very closely nebulously spotted and reticulated. Sometimes it is interrupted-lined with chestnut, with a narrow, light band below the middle. Spire is elevated, rudely gradate, and maculated. Interior of the aperture is light chocolate, with a light band. Size of the shell varies between 13 mm and 63 mm. Compound(s) and Activities Conotoxin: The peptides Contryphan-Vn and Conotoxin-Vn2 extracted from the venom of this marine snail may have potential therapeutic applications, and intensive research is needed to explore the possibilities of utilizing the above conotoxins for the development of new drugs (Spiezia et al., 2013).

Neuroprotective activity: The conopeptide Conotoxin-Vn of this species has been reported to recognize calcium channels through a specific pharmacophore. It is also suggested that Conotoxin-Vn could represent a competitive antagonist of nAChRs (Romeo et al., 2008).

Conus victoriae (Reeve, 1843)

Order: Neogastropoda Family: Conidae Common name: Queen Victoria cone Distribution: Endemic to Australia from Northern Territory to North West Cape, Western Australia Ecology: It lives in depths from intertidal to 10 m on sand and mud, beneath coral rocks, and on exposed or sheltered rocks. Description: Though this species is related to Conus textile, it differs from the latter in its reticulations. These are mostly smaller and arid light-colored, contrasting strongly with the bands of very dark chocolate longitudinal stripes. They are also more or less overlaid with violaceous clouds. Size of the shell varies between 35 mm and 94 mm. C. victoriae is a mollusk-eating cone (molluscivore). Compound(s) and Activities Antinociceptive property: The α-Conotoxin Vc1.1 extracted from the venom of this species possesses antinociceptive actions in animal models of neuropathic pain. This activity is in Phase I (clinical application) (Kumar et al., 2015).

Euchelus asper (Gmelin, 1791)

Order: Seguenziida Family: Chilodontidae Common name: Four-keeled margarite

104

Distribution: Indo-West Pacific Ecology: It is found in intertidal areas under rocks and sandy substrates. Description: Shell of this species is medium sized and thick, whorls are inflated, spire is elevated, and sculpture is composed of granulose, spiral ridges producing a beaded appearance. Aperture is round and columella has a conspicuous tooth at base; outer lip is thick; spiral ridges on dorsal side extend up to margin, thereby providing a toothed appearance; and interior of aperture is iridescent. Color of the shell is deep grayish brown, and umbilicus is not so prominent in adult specimens. Size of the shell varies between 6 mm and 35 mm. Biology Food and feeding: It feeds on green, brown, and red macroalgae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antiangiogenic and antiproliferative activities: The methanolic extract (20 µg/mL) of this species showed moderate but significant cytotoxicity against the A549 non-small-cell lung carcinoma cell line. This cytotoxicity was associated with its apoptotic activity by subG1 phase arrest. Further, the above extract significantly reduced A549 proliferation by reducing the expression of Matrix metalloproteinase-2 (MMP2) and Matrix metalloproteinase-9 (MMP-9). It is therefore suggested that this extract has the potential to inhibit tumor angiogenic and proliferative activity and may be a potential source for the development of new anticancer pharmaceuticals (Agrawal et al., 2017). Others: Ahmad et al.(2018) reported that the whole-body ether extract of this species suppressed phagocytosis in higher concentration in vitro; showed immunosuppressive activity in vivo at the concentrations of 40, 80, and 160 mg/kg; stimulated DTH (delayed type hypersensitivity); reduced the number of plaque-forming cells; and displayed anti-inflammatory activity.

Nerita albicilla (Linnaeus, 1758)

Biology and Ecology of Pharmaceutical Marine Mollusks

Description: Its shell surface is smooth or with slight transverse ridges; it has small pustules and four weak teeth on the columella. Its outer shell color is variegated black and white, occasionally with three conspicuous bands. Interior is white, with a pinkish-gray, granular operculum. N. albicilla grows up to 4 cm, and its maximum reported age is 12 yrs. Biology Food and feeding: It feeds on microalgae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Parasite: This species plays an important role in the transmission of rod-shaped (virgulate) tremade cercariae to fish as a source of zoonotic diseases. Pollution indicator: This species has been reported to serve as pollution indicator as it concentrates trace elements such as Cu, Pb, Zn, Ag, Th, Ba, Tl, S, Sc, and Se (El-Sorogy et al., 2013). Compound(s) and Activities Antibacterial activity: The (methanol) tissue extracts of this species have shown antibacterial activity against the human pathogens Acinetobacter baumannii, P. aeruginosa, and E.  coli K1 (Kiran et al., 2014). The extent of bactericidal activity is given below. Bactericidal activity (%) E. coli K1

P. aeruginosa

Gills

A. baumannii 62.8

34.2

99.1

Gut

77.5

74.3

97.5

Gonad

28.2

84.8

90.0

Source:  Kiran et al. (2014).

Anticancer activity: Traditionally, this species had been used in Kei Island, Southern Maluku, and Indonesia to treat liver disease, including cancer. All extracts of this species contained steroidal and alkaloid compounds, which showed topoisomerase-I inhibitor activities relating to anticancer. The MIC of methanol extract was 2.50 µg/mL. The active compounds of this species could be potential sources for nutraceutical or pharmaceutical development (Hardjito et al., 2012).

Tectus niloticus (Linnaeus, 1767)

Order: Cycloneritida (Neritopsina) Family: Neritidae Common name: Blotched nerite, oxpalate nerite Distribution: Indo-Pacific Ecology: It is commonly found in the intertidal area up to the high-tide zone; on rocky shores, coral reefs, and mangrove trees; depth range 0–7 m. It can also live for a long time away from water, as it stores water within its shell and hence can stand long periods of desiccation.

Order: Trochida

Family: Tegulidae

105

Marine Mollusks

Common name: Commercial top shell, giant top shell snail Distribution: Indo-Pacific (Indian Ocean, New Ireland, New Caledonia, North Australia, French Polynesia, etc.) Ecology: It lives in shallow areas on intertidal reef flats; adults prefer atoll reefs along the reef crest or on reef slopes at depths of 0–20 m. Description: Shell of this species has a conical shape and appears subperforate. It is covered by a corneous, striate brown or yellowish cuticle usually lost on the upper whorls. Its color beneath the cuticle is white, longitudinally striped with crimson, violet, or reddish brown. Base of the shell is maculate or radiantly striate with a lighter shade of the same. Spire is strictly conical. Apex is acute, usually eroded. Shell contains eight to ten whorls; upper ones are tuberculate at the sutures and spirally beaded, and the following ones are flat on their outer surfaces, smooth, and separated by linear suture. Body whorl is expanded, dilated, and compressed at the obtuse periphery and more or less convex below, indented at the axis. Umbilical tract is covered by a spiral, pearly, deeply entering callus. Aperture is transverse and very oblique. Columella is oblique, terminating in a denticle below and with a strong spiral fold above, deeply inserted into the axis. Operculum is circular, thin, corneous, orange-brown, and composed of about ten whorls. Upperside is orangey with slanted brown bars. Underside is white with a pretty spiral pattern of dark red spots. A pair of long tentacles present at the head is brown with three white circles. Length of the shell varies between 50 mm and 165 mm, its diameter between 100 mm and 120 mm. Biology Food and feeding: It feeds on algal biomass, in particular on green turf algae that preferentially grow in rocky areas. Reproduction: Individuals of this species are able to reproduce at about 2 years of age. Females release more than 1 million eggs. It has nocturnal spawning, and the breeding period occurs during spring tides. The eggs, fertilized externally by males, hatch to larval stages. Compound(s) and Activities Antiatherosclerotic activity: This species has been reported to possess bioactive compounds as potential antiatherosclerotic substances (Sarizan, 2013). Further, intensive research is, however, needed on this aspect.

Tectus tentorium (Gmelin, 1791) (=Trochus tentorium) Image not available Order: Trochida Family: Tegulidae Common name: Not designated Distribution: Tanzania, Philippines, Fiji Islands Ecology: It lives in intertidal regions and shallow coastal waters. It is a coral reef–associated species. Description: Shell of this species is longitudinally plicate, especially on the lower part of each whorl. It has strong nodular surface. Sides of the shell are more or less straight. Lower rows of tubercles in each whorl are enlarged; they are much stronger and more pronounced, and the stout fillet that

they form is traversed by strong, thick, oblique, transpirally elongated ribs. Basal surface of the body whorl bears beaded spiral ridges. Columella is distinctly denticulated. Shell is marked with transpiral reddish bands, but they are much closer together and are often broken up into patches that are darker and more conspicuous in the lower part of each whorl. Biology Food and feeding: It feeds on algal biomass, in particular on green turf algae that preferentially grow in rocky areas. Reproduction: Not reported. Compound(s) and Activities Antibacterial activities: The acetone crude extract of the whole body of this species showed better antibacterial activities. Maximum antibacterial inhibition zone was with S. pneumoniae and K. pneumoniae; and the minimal inhibitory concentration was recorded with E. coli, S. pneumoniae, Staphylococcus aureus, and V. cholerae. (Datta et al., 2015). Anti-inflammatory and analgesic effects: At the extract concentration of 25 and 50 mg/kg (p.o), this species showed significant decrease in paw thickness (41.15% and 73.6%, respectively) at the 5th hour of the experiment. The 100% fraction of this species (200 mg/kg p.o) exhibited significant inhibition of 79.22% against acetic acid–induced abdominal constrictions. The dose of 25 mg/kg showed 67.86% inhibition of writhing (Chellaram et al., 2012). The 100% acetone fraction of this species also showed analgesic effects, as detailed below. Treatment

% Inhibition of Writhing

25 mg/kg p.o

67.9

50 mg/kg p.o

79.2

Source:  Chellaram et al. (2012).

Pati et al. (2015) reported that the 100% acetone extract of this species showed anti-inflammatory activity in albino rats. The 100% acetone fraction of crude extract (25 and 50 mg/kg) of this species showed anti-inflammatory activity by inhibiting acetic acid–induced abdominal constrictions. Further, this extract inhibited writhing and decreased paw thickness (Ahmad et al., 2018).

Tegula gallina (Forbes, 1850)

Order: Trochida (Archaeogastropoda)   Family: Tegulidae

106

Common name: Speckled tegula Distribution: East Pacific: from Santa Barbara County, California to Baja, California Ecology: It is a reef-associated species inhabiting intertidal rocks. Description: Shell of this species is imperforate, heavy, solid, and thick. It has a conoidal shape and is elevated. Its colors show alternating whitish and purplish-gray or blackish crowded, slanting axial stripes. Stripes occupy the interstices between close, narrow superficial folds of the surface, which may be well marked or obsolete; and continuous or cut into granules by equally close spiral furrows. Its five to six whorls are convex and rough and usually indented a short distance below the suture. Spire is conoidal. Apex is usually blunt, eroded, and yellow. Body whorl is rounded at the periphery. Convex base often has an eroded area in front of the aperture. Oblique aperture is nearly round. Outer lip is black-edged, smooth, and pearly within. Columella is short, arcuate, and strongly bidentate near the base. Place of the umbilicus is marked by a pit. Shell is 1.9–4.1 cm high and wide, though it may be slightly higher than wide. Biology Food and feeding: It is a herbivore grazing on macroalgae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antiviral activity: The unidentified bioactive macromolecules derived from the organic extracts of this species showed antiviral activity (Dang et al., 2011).

Trochus radiatus (Gmelin, 1791)

Biology and Ecology of Pharmaceutical Marine Mollusks

shell is yellowish whitish, tinged with green, and radiantly striped with broad or narrow uninterrupted, axial, crimson flames. Base of the shell is white or pink, radiantly marked or minutely speckled with red. Aperture, columella, and umbilical area are pearl white. Spire has nearly straight outlines. Apex is acute, generally eroded, and orange-colored. There are seven whorls, which are planulate, sometimes a little concave in the middle. Body whorl has a sharply angled periphery. Shell upper surface is circled by irregularly beaded bands, five or six on each whorl, uneven in size; upper row is largest. Bead in each whorl is larger on the upper row than those on lower rows. Base of the shell is nearly flat, concentrically lirate. These lirae are granulose, rather coarse, with broad interspaces, which are frequently occupied by revolving lirulae or striae. Oblique columella is strongly plicate above, and its edge is nearly smooth and shows blunt teeth. Large aperture is subrhomboidal, lirate within, and grooved. Basal lip is thickened and crenate. Umbilicus is wide and deep. Umbilical tract is funnel-shaped and rather broad, with a central rib. Its length varies between 17 mm and 40 mm. Biology Food and feeding: These animals browse on detritus and algae, and they sometimes filter feed. Reproduction: Sexes are separate in this species. Its sex ratio was generally 1:1. Females are found to be slightly more numerous than the males. Male gonads are pale brown to creamy white in color, and mature female gonads are dark green. They release their gametes (eggs and sperm) directly into the water, and fertilization is external. The eggs are lecithotrophic (containing a yolk). It reaches its first maturity at a size of 18.7 mm. Peak period of spawning is during November, and a secondary peak was in April (Anon., http:​// sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​36803​/13/1​3_cha​ pter%​207.p​df). Compound(s) and Activities Antibacterial activity: The crude methanolic extracts of this species displayed antibacterial activity against E. coli (Babar et al., 2012).

Lunella coronata (Gmelin, 1791) (=Turbo coronatus)

Order: Trochida Family: Trochidae Common name: Radiate top shell, banded trochus Distribution: Indian Ocean off Madagascar and in the Western Pacific Ecology: It inhabits intertidal rock boulders and mangroves. Description: Its thick, rather solid, trochoidal shell has a moderately elevated spire and is false-umbilicate. Color of the

Order: Trochida

Family: Turbinidae

107

Marine Mollusks

Common name: Crowned turban shell, coronate moon turban, horned turban Distribution Red Sea, off Southeast Africa, Mascarene Basin, and in Indo-Pacific Ecology: It is found in the intertidal to immediate subtidal rocky shores; upper eulittoral zone, in pools or under stones; depth range 0–1 m. Description: Solid, imperforate shell of this species has a depressed-turbinate shape with a diameter greater than the altitude. It is covered with an irregular spiral series of nodules and granules, of which the subsutural series and two on the median portion of the body whorl are more prominent. Spire is depressed and dome-shaped, with an apex that is frequently eroded and red. Shell contains four to five whorls, the last very large. Large aperture is round and iridescent within. Wide columella is flattened and excavated, deflexed, recurved, and somewhat channeled at its base. Inside of the operculum is flat, greenish, and golden; iridescent, with about five to six whorls; and has a subcentral nucleus. Its outside is convex, greenish, and sparsely granulate all over. Shell grows to a length of 4 cm. Biology Food and feeding: It is herbivorous, consuming small epibenthic algae and vegetable detritus. Reproduction: It is a dioecious species with a sex ratio of 1:1. Animal attains sexual maturity in Transkei coast (South Africa) at a shell height of 16 mm. In this coast, ripe, prespawning individuals comprised a major proportion of the population in December and January. A distinct peak in the spawning activity of T. coronatus was evident between December and February. The presence of individual T. coronatus at various developmental stages in the monthly samples, coupled with low levels of breeding activity throughout the year, suggests that this species may have an extended breeding season with multiple spawning (Lasiak, 1986). Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults (Lasiak,1986). Compound(s) and Activities Anticancer/cytotoxic activity: The organic extracts of this species showed anticancer activity against breast cancer cell lines MDAMB468 and T47D and animal (NIH/3T3) and human (MCF10A) normal cell lines. After determining the lethal concentration of 50% of the cells (LC50), ethyl acetate fraction had the strongest effect on cell line MDA-MB468 (LC50 equal to 12.0 µg/ml), and chloroform fraction had the strongest effect on the cell line T47D (LC50 equal to 19.8 µg/ml) (Honari et al., 2017).

Turbo bruneus (Röding, 1791)

Order: Trochida Family: Turbinidae Common name: Brown (Pacific) dwarf turban, little burnt turbo, dwarf turban snail Distribution: Indo-West Pacific: from Madagascar and India to eastern Indonesia; north to the Philippines and south to northern Australia Ecology: It inhabits rocky shores; also found in shallow subtidal waters. Description: Shell of this species is thick with spiral cords, which feel rough as they have tiny scales. Chalky operculum is hemispherical with many tiny bumps; it is dark green with grayish and white margins. Body has brown mottles and a pair of slender tentacles. Length of the shell varies between 20 mm and 60 mm. Biology Food and feeding: It is herbivorous, consuming small epibenthic algae and vegetable detritus. Reproduction: Annual cycle of reproduction of this species from the southeast coast of India showed that the overall male and female ratio in this species was found to be 1: 0.96. Both sexes of T. brunneus attain sexual maturity between 23 and 27 mm. The gonadal index (GI) values for both the sexes were generally low. Spawning occurred during June–September, when the seawater temperature was comparatively higher. The limited percentage of matured oocytes that existed even after spawning indicated the high possibility of partial spawning in this species (Ramesh et al., 2010). It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Anti-inflammatory, antioxidant, analgesic, and antimicrobial activities: The bioactive compound 6-(di​pheny​lphos​phory​l)-3,​ 4-bis​(diis​oprop​ylami​no)-5​-pyrr​olidi​no pyridazine isolated from this species showed anti-inflammatory, antioxidant,

108

Biology and Ecology of Pharmaceutical Marine Mollusks

analgesic, and antimicrobial activities (Muthu and Selvaraj, 2015). Antioxidant and antimicrobial properties: The bioactive compound 3,3,4​,4-te​tracy​ano-5​,6-di​pheny​l-2-(​cyclo​hexyl​ imino​)-2,3​,4,5-​tetra​hydro​pyrid​ine isolated from this species showed antioxidant and antimicrobial activities. Further, it is a neuroprotective agent used to prepare medicines for treating disease causing demyelination (Muthu and Selvaraj, 2015). Antimicrobial activities: The bioactive compound 1H-pu​ rin-6​-amin​e,[(2​-fluo​rophe​nyl)m​ethyl​]-(CA​S) isolated from  this species has been found to possess antimicrobial and antifungal activities. Further, its derivatives are also known to possess antitubercular, anti-inflammatory, antitumor, amoebic, antiparkinsonian, anthelmintic, antihypertensive, antihyperlipidemic, antiulcer, chemoprotective, and selective CCR3 receptor antagonist activity (Muthu and Selvaraj, 2015). Antiandrogen, antiplatelet agent, antitubulin, and antimicrobial properties: The bioactive compound 3-(4-​chlor​ophen​ yl)-4​,6-di​metho​xy-1-​(prop​-2′-e​ nyl) indole-7 carbaldehyde isolated from this species has been found to possess antiandrogen, antiplatelet agent, antitubulin, and antimicrobial properties (Muthu and Selvaraj, 2015). The presence of various bioactive compounds justifies the potential use of the meat of this species for various diseases. Further investigations on the purification and chemical elucidation of the above bioactive compounds pave the way for the development of new drugs in the future. Others: Muthu and Selvaraj (2015) also reported on the occurrence of eight compounds, viz. 6-(Di​pheny​lphos​phory​ l)-3,​4-bis​(diis​oprop​ylami​no)-5​-pyrr​olidi​no pyridazine, cyclohexasiloxane dodecamethyl-(CAS), 3,3,4​,4-Te​tracy​ano-5​ ,6-di​pheny​l-2-(​cyclo​hexyl​imino​)-2,3​,4,5-​ tetrahydropyridine, 2,4-bis(trimethylsilyl)-1,3 dithietane-1,3,3-tetraoxide, octadecamethylcyclononasiloxane, 1H-Pu​rin-6​-amin​e,[(2​-fluo​ rophe​nyl)m​ethyl​]-(CA​S), 3-(4-​chlor​ophen​yl)-4​,6-di​metho​ xy-1-​(prop​-2’-e​nyl) indole-7 carbaldehyde, and epinephrinetetratms (L-Adrenaline, 4TMS derivative) from this species. The pharmaceutical activities of these compounds are, however, as yet unknown.

O​ctade​camet​hylcy​clono​nasil​oxane​

1H-Pu​rin-6​-amin​e,[(2​-fluo​rophe​nyl)m​ethyl​]-(CA​S)

Ep​ineph​rine-​tetra​tms (L-Adrenaline, 4TMS derivative)

Turbo marmoratus (Linnaeus, 1758)

  Cyclohexasiloxane dodec​ameth​yl-(C​AS)​

Order: Trochida Family: Turbinidae Common name: Green turban, marbled turban, great green turban, green snail

109

Marine Mollusks

Distribution: Indian Ocean: off Tanzania, Madagascar, Aldabra, and Mascarene Basin; western Pacific oceans; off Queensland, Australia; introduced in French Polynesia Ecology: It inhabits rocks of subtidal areas and crevices on the crests and outer slopes of shallow coral reefs to depths of 20 m below surface; depth range 1–30 m. Description: Large, imperforate, solid shell of this species is ventricose and as broad as it is long. Its color pattern is green, marbled with white and rich brown. Its six to seven whorls are flattened or concave above, rounded and bearing two nodose keels below and a stronger nodose carina above. It bears blunt tubercles, especially strong on the shoulders. Its large, circular aperture has a golden, pearly shine. Columellar region is more or less excavated. It attains a maximum length of 22 cm. Biology Food and feeding: It is a nocturnal species, searching for and feeding on algae at night. Reproduction: In Japanese seas, the green snail had sex ratios of 1:1. The number of oocytes per unit weight was significantly different among different portions of an ovary. The main spawning season of this species was August–November and July–November in the two areas studied. Mature individuals were found during all seasons in both localities (Komatsu et al., 1995). Compound(s) and Activities Neuroprotective activity: The ethyl acetate extracts of this species containing the terpenoid compounds showed neuroprotective activity with cholinesterases (ChEs) and AChE inhibitory activities. The diiodotyramine derivative turbotoxin A of this species showed AChE inhibitory activity with an IC50 value of 28 µM (Grosso et al., 2014). Toxicity: The aqueous ethanol extract of the viscera of this species yielded two toxins, viz. turbotoxins A and B, which exhibited acute toxicity against ddY mice, with LD 9 9 values of 1.0 and 4.0 mg/kg, respectively (Kigoshi et al., 1999).

Turbo setosus (Gmelin, 1791)

Order: Trochida Family: Turbinidae Common name: Rough turban Distribution: Indian Ocean: off Madagascar, the Mascarene Basin, and Mauritius; in the Central and Southwest Pacific; off Australia Ecology: It is found in sublittoral zones; shallow water; exposed areas of coral reefs; intertidal to 5 m. Description: Solid, imperforate shell of this species has an ovate-pointed shape. Its color pattern is whitish or greenish, maculated with brown and olive. Its conic spire is acute. All the six whorls are convex, striate, and spirally lirate. Ridges are unequal, wider than the interspaces, frequently with interstitial lirulae. Large aperture is oval and white within. Outer lip is frequently green-tinged and is fluted. Columella is arcuate, deflexed, and dilated at its base. Biology Food and feeding: It is herbivorous and a detritus feeder, feeding on detritus and algae. Reproduction: It is a broadcast spawner. Embryos develop into planktonic trocophore larvae and later into juvenile veligers before becoming fully grown adults. Compound(s) and Activities Antioxidant activity: The crude organic extract of this species contains alkaloids, flavonoids, steroids, and triterpenoids (n-hexane, ethyl acetate, and methanol). The ethyl acetate of this extract has been reported to possess antioxidant activity with an IC50 value of 1578.43 ppm (Merdekawati, 2013).

Turbo stenogyrus (Fischer, 1873)

Turbotoxin A

R=H; X=CF3COO Turbotoxin B

Order: Trochida Family: Turbinidae Common name: Miniature turban

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Biology and Ecology of Pharmaceutical Marine Mollusks

Distribution: Southwest Pacific and off Japan and Indonesia Ecology: It inhabits rocky shore areas. Description: Its acute, elongate, imperforate shell has an ovate-conic shape. All the six whorls are rounded, transversely lirate, radiate, and finely striate. Suture is margined. Lirae are narrow. Shell has flat ribs below. Interstices and below the suture are striate. Circular aperture is silvery within. Columella is regularly arcuate and is not produced at its base. Color pattern of the shell is pale green with chestnut maculations, and lirae are white and brown articulated. Length of the shell varies between 10 mm and 35 mm. Biology Food and feeding: It feeds on a combination of different algal species. Reproduction: Not reported.

Turbostatin 2

Compound(s) and Activities Anticancer activity: The glycosphingolipids viz. turbostatins 1–4 isolated from this species exhibited significant (GI50 0.15−2.6 μg/mL) cancer-cell growth inhibition against the murine P388 lymphocytic leukemia and a panel of human cancer cell lines (Pettit et al., 2005).

Turbostatins Cancer Cell Line

1

2

3

4

P388

0.27

0.15

0.25

0.29

BXPC-3 MCF-7 SF268 NCI-H460 KML20L2

0.71 0.44 0.98 0.34 0.35

1.0 0.39 1.9 0.53 0.35

1.6 0.48 1.9 0.55 0.48

0.93 0.44 1.5 0.49 0.41

DU-145

1.6

1.7

2.6

2.6

Turbostatin 3

Source:  Pettit et al. (2005). Cancer type: P388 (lymphocytic leukemia); BXPC-3 (pancreas adenocarcinoma); MCF-7 (breast adenocarcinoma); SF268 (CNS glioblastoma); NCIH460 (lung large cell); KM20L2 (colon adenocarcinoma); DU-145 (prostate carcinoma).

Turbostatin 4

Turbostatin 1

Ciavatta et al. (2017) reported that the cerebrosides turbostatins A–D (1–4) showed anticancer activity against murine and human cancer cell lines with GI50 values ranging between ∼0.2 and ∼4 μM.

111

Marine Mollusks

Thuridilla hopei (Verany, 1853)

biological activities, including antimicrobial and anti-inflammatory properties; and antiarrhythmic activity.

Epoxy​lacto​ne

Order: Sacoglossa Family: Elysiidae Common name: Hope’s Elysia Distribution: Mediterranean Sea; off Spain, Portugal, and Greece Ecology: It lives from the lower intertidal down to a depth of about 35 m, and is generally found crawling on hard substrate. Description: Animal is dark brown to blue in ground color, with a bright orange marginal band on the parapodia. Stripes and/or spots on the outer parapodial surface and head are white, yellow, and/or light blue. Inner parapodial surface is iridescent blue, and the parapodial flaps are held over the body in life. Parapodial color pattern is highly variable in this species. Rhinophores are rolled and large with a white stripe merging at the head to form a “Y” shape. Pericardium is short and round with (usually) one pair of dorsal vessels branching from its posterior side. Sole of the foot has a transverse division that divides it. It is about 2 cm in length. Biology Food and feeding: It feeds exclusively on the green algae of the genus Caulerpa. Reproduction: The species is hermaphroditic. The reproductive tract opens on the right side of the animal, almost at the rear base of the right rhinophore, which implies head-tohead contact of the partners (even if the bodies intermingle). The penis, a rare and notable thing among the sacoglosses, is bright red. The color of the spawn fades as embryonic development progresses. The eggs are attached to the base of calcareous algae or green algae such as Flabellia petiolata. Larval development is lecitotrophic (the larvae feed on the reserves contained in the egg). After 20 days (at 21 ° C), the veliger larvae will hatch and their development will continue until the adult stage (Anon., DORIS, http:​//dor​is.ff​essm.​fr/Es​ peces​/ Thur​idill​a-hop​ei-Th​uridi​lle-d​e-Hop​e-955​). Compound(s) and Activities Bioactivities: The acetone extract of this species yielded compounds such as epoxylactone, nor-thuridillanol, dihydronor-thuridillanol, deacetyl-dihydro-nor-thuridillanol, thuridillin A, thuridillin B, and thuridillin C (Carbone et al., 2014). These compounds are believed to possess significant

No​r-thu​ridil​lanol​ 

  R=Ac Dihy​dro-n​or-th​uridi​llano​l

R=H Deace​tyl-d​ihydr​o-nor​-thur​idill​anol

Thuri​dilli​n A

Thuridillin B

Thuridillin C

 

112

Thuridilla splendens (Baba, 1949)

Order: Sacoglossa Family: Elysiidae Common name: Not designated Distribution: Australia, Vanuatu, Solomon Islands, Papua New Guinea, and Japan Ecology: It is found in coral reefs at depths of 2–12 m. Description: This species has a greenish body color with yellow spots and lines. There is a series of blue or greenish spots below the alternating black and yellow lines along the parapodial margin. It has a length of 30 mm. Biology Food and feeding: It feeds mainly on sponges. Reproduction: Not reported. Compound(s) and Activities Antimicrobial and anti-inflammatory properties: Metabolites such as thuridillin A, thuridillin B, and thuridillins D–F with antimicrobial and anti-inflammatory properties have been isolated from this species (Somerville et al., 2012).

Biology and Ecology of Pharmaceutical Marine Mollusks

neck are bare, apart from two tentacles folded along the sides of the head. Body is wider at the front and tapers to a point at the rear, and it lacks a distinct foot. Mouth lies underneath. Running along the length of the body on each side is a veiny green winglike membrane (parapodium) with black and gold margin. Laterally, it can measure 6.35 cm (2.5 in) across with wings expanded. Kelaart wrote, “The whole animal gives one the idea of a large leaf and, when moving, that of a butterfly,” adding that the pulsating heart was visible in the middle of its back. It grows to a very large size of 12 cm. Biology Food and feeding: It mainly feeds on siphonous or siphonocladous green algae. Reproduction: Elysia species are simultaneous hermaphrodites and possess complex reproductive systems for internal crossfertilization, typically donating and receiving sperm reciprocally in a head-to-tail position. Hypodermic insemination, in which sperm is injected through the partner’s body surface, is widespread, and can be unilateral or bilateral. Compound(s) and Activities Cytotoxicity: Cyclic depsipeptide derivatives, viz. kahalalides D, F, R, and S, have been isolated from this species. Among them, kahalalide R was found to exert comparable or even higher cytotoxicity than the potential drug candidate kahalalide F towards the MCF7 human breast carcinoma cell line (Ashour et al., 2006).

Elysia grandifolia (Kelaart, 1858)

Order: Sacoglossa Family: Elysiidae Common name: Not designated Distribution: Indo-Pacific; native to the waters off southern India and Sri Lanka; colonized eastern Mediterranean Sea Ecology: It is a demersal species, common in brackish waters. Description: E. grandifolia has a light-green head and body, marked with white, and more rarely black, spots. Head and

Kahalalide R; R=H Kahalalide S; R=OH

113

Marine Mollusks

Elysia nisbeti (Thompson, 1977)

Order: Sacoglossa Family: Elysiidae Common name: Not known Distribution: Jamaica, Bermuda Ecology: It inhabits mangroves. Description: Body of this species is slender and rich green in color, and foot is pale yellow-green. Rhinophores are dark olive-green, sometimes arched backwards over dorsum and held in this position. Dorsal surface of head is with conspicuous pale brown blotches forming a “Y” shape that extends up rhinophores. Oral lobes are shelflike with darkbrown edges and white pustules. Parapodial margin is pale brown, thickened, and swollen at intervals with white vesicles. Parapodial sides have black specks. Rows of low white papillae run along body and up rhinophores. It has a size range of 5.5–10 mm. Biology Food and feeding: It feeds primarily on algae by piercing and sucking algae cells (chloroplasts). Reproduction: Not reported.

Elysia ornata (Swainson, 1840)

Order: Sacoglossa Family: Elysiidae Common name: Ornate elysia, ornate leaf slug, ornate sapsucking slug Distribution: Circum-tropical: Caribbean and Indo-West Pacific Ecology: It inhabits shores. Description: Body of this species is long with a pair of very large “wings” (called parapodia). Overall body color of the slug may be shades of green, yellow, or even white. Color of the slug depends on how much and what seaweed is in the animal’s digestive system, but all have a black margin on the edge of the parapodia, with an orange or yellow margin next to the black. There is a pair of long thick tentacles with tips in the same color banding as the body edge. Body may have black spots. It may also have white spots, which are glands that secrete a white substance that may repel predators. Parapodia are often held in ruffles so that the animal resembles seaweed. It has a size range of 4–6 cm. Biology Food and feeding: It feeds primarily on green algae. Reproduction: It lays clutches of egg capsules. Development is planktotrophic. A characteristic of this species is the presence of multiple embryos developing within some capsules. All embryos develop and hatch as veliger larvae.

Compound(s) and Activities Anticancer activity: The sesquiterpene, caulerpenyne, of this species showed anticancer activity. This compound induces aggregation of tubulin, which may be responsible for the inhibition of tubulin polymerization and bundling of residual microtubules. Caulerpenyne has also been reported to block the stimulation of mitogen‐activated protein kinase (MAPK), which contributes to the control of cell functions such as proliferation, differentiation, and death. The average GI50 for caulerpenyne is ∼10 μM in various cancer cell lines. The GI50 value reported by the NCI for caulerpenyne in the 60 cell line pane l is ∼40 μM (Ciavatta et al., 2017).

Compound(s) and Activities Antimicrobial/anticancer property: The CHCl3-MeOH extract of this species yielded kahalalide F, kahalalide Z1, and kahalalide Z2. Among these compounds, kahalalide Z1 and kahalalide Z2 displayed significant antimicrobial properties against several species of fungi. However, all the above three compounds were found to inhibit the in-vitro growth of a series of cancer cell lines (Ciavatta et al., 2017).

Caulerpenyne

Kahalalide F

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Biology and Ecology of Pharmaceutical Marine Mollusks

across side of head under large eyespots, up onto proximal portion of each rhinophore. Rhinophores are elongated, rolled, thick, with rounded blunt tips. Outer surface of rhinophores is covered with white rounded papillae, both large and small. A thick brown transverse band divides proximal third of each rhinophore from the distal two-thirds. Its maximum reported size is 20 mm in length.

Kahalalide Z1

Biology Food and feeding: It feeds on algae in the Ulvophyceae, including species of Penicillus and Bryopsis. Reproduction: Development in E. patina is lecithotrophic. Eggs are laid in a typical elysiid spiral, one egg per capsule. Veliger larvae released from the eggs swim actively for 4 days before undergoing metamorphosis. Larvae release white mucus when disturbed. Compound(s) and Activities Anticancer activity: As for E. nisbeti (Ciavatta et al., 2017).

Elysia rufescens (Pease, 1871)

Kahalalide Z2

Elysia patina (Ev. Marcus, 1980)

Order: Sacoglossa Family: Elysiidae Common name: Not designated Distribution: Florida, the United States; Bahamas: Sweetings Cay, Grand Bahamas Island; Stirrup Cay; Northern Exumas; Bimini, Mia Reef Isla Mujeres, Mexico Ecology: This benthic species is found on submergent vegetation; depth range 0–5 m. Description: Overall color of this species is mottled white, gray, or yellowish-brown, with scattered brown patches on sides of head and parapodia. Body is elongated when crawling. Head is predominantly white. A thin brown line runs

Phylum: Mollusca Class: Gastropoda Order: Saccoglossa Family: Elysiidae Common name: Not designated Distribution: Indo-Pacific; South Africa, Réunion, Thailand, Myanmar, Philippines, Japan, Guam, Samoa, Tahiti, Hawaii, and Australia Ecology: These animals are often found associated with the green algae Bryopsis pennata. It has both sedentary and migratory forms. It occurs from the low intertidal to about 3 m. Description: Body of the animal is olive green with large white spots, often in a reticulated pattern. Sedentary form has tall, thin parapodia containing elaborate ramifications of the digestive gland. Parapodia usually meet in a more or less continuous line without obvious chimneys and are olive-brown with closely spaced cream patches. There is a continuous violet-black marginal line and an orange submarginal line. Rhinophores are olive-brown with cream patches and violetblack tips. Migratory form is with lower and proportionately thicker parapodia that are typically held in three chimneys. Unlike in the sedentary form, the migratory forms contain

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relatively few branches of the digestive gland but are otherwise similar in color. Migratory forms are usually smaller (less than 3 cm), and sedentary form reaches a maximum size of 6 cm. Biology Food and feeding: It feeds mainly on green algae, Bryopsis spp. Reproduction: Not reported. Compound(s) and Activities Anticancer activity: This species has yielded several novel peptides, viz. kahalalides. Among these compounds, kahalalide F is known to exhibit interesting antitumor activity. Kahalalide F has shown in-vitro and in-vivo selectivity for prostate-derived cell lines and tumors. It has been observed that kahalalide F induces disturbances in lysosomal function that might lead to intracellular acidification and cell death. In phase I clinical trials, kahalalide F exhibited clinical benefits in treated patients. It is also suggested that kahalalide F may be active against other tumor types and deserves further clinical testing, either as a single agent or in combination. Currently, this agent is undergoing phase II clinical trials for the treatment of lung and prostate cancers and melanoma (Hamann and Scheuer,1993; Suarez-Jimenez et al., 2012). Blunt et al. (2016) reported on the occurrence of peptides kahalalides F, Y with anticancer activity in this species. Hamann et al. (1996) reported that the Cyclic depsipeptides kahalalides A -F, G, K, and V -Y have been isolated from this species (Hamann et al., 1996; Rao et al., 2008). Kahalalide A showed in-vitro activity against Mycobacterium tuberculosis H37Rv with 83% inhibition at 12.5 g/mL (Gal and Ulber, 2005). Kahalalides A, B, G showed activity against cancer and AIDS (Faircloth and Marchante, 2006). Kahalalide E showed selective activity against herpes simplex II virus (HSV II) (Gao and Hamann, 2011). Kahalalide F showed several activities as detailed below 1. Anticancer activity: Selectivity against solid tumor cell lines: IC50 values of 2.5, 0.25, and 10 μg/mL. 2. against P-388 and KB, respectively; and active against CV-1 cells with an IC50 value of 0.25 μg/ mL (Gao and Hamann, 2011); against U prostate and breast cancer cell lines; and potent cytotoxicity and induction of necrosis (Mayer and Gustafson, 2006) 3. Antiviral activity: 0.5 μg/mL (95% reduction) with HSV II using mink lung cells (Gao and Hamann, 2011). 4. Antifungal activity: IC50 values of 3.02 μM against C. albicans;1.53 μM against Candida neoformans, and 3.21 μM against A. fumigatus (Gao and Hamann, 2011).

5. Immunosuppressive activity: IC50 of 3 μg/mL in a mixed lymphocyte reaction assay, IC50 of 23 μg/mL with lymphocyte viability (Gao and Hamann, 2011). 6. Antileishmanial activity: LC50 values of 6.13 μM against Leishmania onovani; and 8.31 μM against Leishmania pifanoi (Gao and Hamann, 2011).

Kahalalide A

Kahalalide B

Kahalalide C

Kahalalide D

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Kahalalide Y

Kahalalide E

Others: The following marine drugs derived from this species are in clinical trials (Ruiz-Torres et al., 2017).

Clinical Status

Compound Name

Phase II

Glembatumumab vedotin

Breast cancer and melanoma

Targets glycoprotein NMB (a protein overexpressed by multiple tumor types)

Phase I–II

Elisidepsin

Anticancer

Antineoplastic agent, modifying lipids from cell membrane

Disease Area

Kahalalide G

Mode of Action

Elysia subornata (Verrill, 1901)

 

    R=OH   Kahalalide K             Kahalalide V

 

     R-OH   Kahalalide W              Kahalalide X

Order: Sacoglossa Family: Elysiidae Common name: Not reported Distribution: Western Atlantic: Florida, Caribbean, Brazil Ecology: This benthic species is found on submergent vegetation; depth range 0–4 m. Description: This species is highly variable in color, ranging from yellow green, to dusky olive, to reddish, usually with brownish to black parapodial margins (pale or absent in some specimens). Parapodial margin is thickened and whitish. Parapodia are minutely papillose and often have white spots, sometimes with black rings. Rhinophores are papillose and

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have bands of white, gray, and/or brown. It grows to a maximum length of 7.0 cm.

Plak​obran​chus-​ocell​atus-​a.htm​l). No other information is available.

Biology Food and feeding: It mainly feeds on Caulerpa taxifolia (Chlorophyta). Reproduction: Not reported.

Compound(s) and Activities Bioactivities: The ethanolic extract of this species showed compounds such as pentadecanoic acid-14-methyl ester, hexadecanoic acid-ethyl ester, octadecanoic acid-Methyl ester, 10-Hydroxy,5,7Dimethoxy-2,3-Dimethyl-1,4-Anthracene Dione, Pregnane trione, Benzopyran-9-methanol, tetrahydro-hydroxy, dimethyl-3-pentyl, 10,13- Dimethyl 3-oxa Doceca hydro Cyclopenta phenantharanyl ester, AndrostenEthynyl-3,17-Diol Oxandrosta-11,5-Diene-3-One, Methyl,2,3Hydroxy- 5,7,9-estratiene-17-yl-propionate, Retinoic acid, methyl ester, and Carbamic acid-methylene-Di 4,1- Phenylene Bis-Di methyl ester. The major compounds identified have shown cancer-preventive, antioxidant, hypochloesterolemic, nematicide, pesticide, lubricant, antiandrogenic, and hemolytic activities (Devi and Revathi, 2015).

Compound(s) and Activities Anticancer: As for E. nisbeti (Ciavatta et al., 2017).

Plakobranchus ocellatus (van Hasselt, 1824)

  Pentadecanoic acid-14-methyl ester Hexadecanoic acidethyl ester Order: Sacoglossa Family: Elysiidae Common name: Ringed sap-sucking slug Distribution: Indo-Pacific: Big Island, Maui, Oahu, Kauai, French Frigate Shoals, Midway, and Kure Ecology: It occurs in highly protected to moderately protected back reef areas, sandy and mixed habitats, and in Halimeda kanaloana beds at depths from < 1 to 18 m. Active crawling and mating are often crepuscular, with the animals spending much of the time, both by day and night, resting passively on the bottom with a fine layer of sand covering their bodies. Description: Body of this photosynthetic slug is broad, truncate, and dorsoventrally flattened, with broad parapodia that meet in the center of the notum and rhinophores that extend laterally. Its translucent, gray-cream body is decorated with yellow-centered and blue-centered ocelli, and there are purple highlights on the rhinophore tips and posterior margin. Beneath the parapodia are longitudinal green ridges. It attains a maximum size of 6.4 cm. Biology Food and feeding: These animals feed on a broad food spectrum, including members of the genera Halimeda, Caulerpa, Udotea, and Acetabularia, with an emphasis on Halimeda macroloba. Interestingly, chloroplasts derived from their food are retained in the ridges beneath their parapodia and may provide much of their nutrition. Reproduction: In this species, the egg mass is a cream, irregular spiral with a ribbon diameter of about 1 mm. It is typically laid on algae such as Halimeda and Acanthophora (Pittman and Fiene, http:​//sea​slugs​ofhaw​aii.c​om/sp​ecies​/

Octadecanoic acid-Methyl ester

10-Hydroxy,5,7- Dimethoxy-2,3-Dimethyl-1,4-Anthracene Dione

      Retinoic acid, methyl ester     Carbamic acid-methylene-Di 4,1-Phenylene Bis-Di methyl ester Antifungal activity: The crude extracts of this species showed antifungal activity against C. albicans, C.

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parapsilosis, and C. glabrata, with inhibition zones of 30.18, 35.12, and 34.12 mm, respectively (Oliaei et al., 2015). The methanolic crude extract (50 μL) of this species displayed maximum inhibitory zone against S. flexneri (22 mm) and S. aureus (19 mm); moderate activity against S. typhi (15 mm), K. pneumoniae (14 mm), and S. flexneri (14 mm); and less activity against S. aureus (9 mm) (Reddy et al., 2015).

Cyerce nigricans (Pease, 1866)

Biology and Ecology of Pharmaceutical Marine Mollusks

Chlorodesmin Others: The compounds pyrone 1 and pyrone 2 have been isolated from this species. These compounds come from cyclization of linear precursors following polypropionate biosynthesis. The activities of these compounds, however, are presently unknown (Roussis et al., 1990).

  Order: Sacoglossa Family: Caliphyllidae Common name: Black and gold sapsucking slug, black cyerce Distribution: Pacific Ocean and Indian Ocean Ecology: It occurs in reef flats. It is one of the “icon” species of the Great Barrier Reef. Description: Cerata (blade or leaflike projections or tentaclelike appendages present on the dorsal side of the animal, used in respiration, defense, and digestion) of this species are basically black and gold. Margin of each cerata is vivid white, and below that is usually a golden band. Below that again are many golden spots. Its long bifurcated rhinophores are black with pale longitudinal lines extending up both forks. Its maximum length is 4 cm. It produces distasteful secretions that are easily cast through the cerata (appendages) when the animal is disturbed. Biology Food and feeding: It mainly feeds on the green algae Chlorodesmis fastigiata. These animals do not hold chloroplasts from the algae they eat in their cerata. Also, the algal chloroplasts they do ingest are not retained and therefore do not photosynthesize inside the animal. Reproduction: It is a hermaphrodite. Fertilization is internal, and it lays a flat white spiral egg mass on the substrate. The veliger larva has a shell, which disappears in the juvenile. Compound(s) and Activities Cytotoxic, antibacterial, and antifungal activities: A modified diterpene compound, chlorodesmin, with antibacterial and antifungal activities has been isolated from this species (Fisch et al., 2017; Roussis et al., 1990).

           Pyrone 1              Pyrone 2

Onchidium sp. (1)

Order: Systellommatophora Family: Onchidiidae Common name: Onch slug, air-breathing sea slug Distribution: Not reported as it is an unidentified species. Ecology: It lives on algae-covered rocks or other hard surfaces, or on mud in mangroves or mangrove tree roots. They are often well hidden, especially on a hot day, and are well camouflaged even when moving about in the open. Biology: These shell-less mollusks have tough leathery skin, a broad foot, and tiny eyes at the tips of a pair of long fleshy stalks. Most snails have eyes at the base of tentacles. Size of the animal varies from 1 to 5 cm. Biology Food and feeding: It feeds primarily on microalgae. Reproduction: Not reported.

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Compound(s) and Activities Cytotoxicity: The onchidione analogues (A–D) and ilikonapyrone esters (E–J) isolated from this unidentified species have shown mild cytotoxicity (Blunt et al., 2016).

Onchidium sp. (3) Compound(s) and Activities Anticancer activity: The lipophilic extract of this species containing 3‐ace​tyl‐1​1‐(3‐​methy​lbuta​noyl)​‐13‐p​ropan​oylil​ikona​ pyron​e showed growth inhibitory activity in a minipanel of six human cancer cell lines: A549 NSCLC, MCF‐7 breast cancer, PC‐3 prostate cancer, Hs683 oligodendroglioma, U373 glioblastoma, and SKMEL‐28 melanoma, with Gi50 values ranging from 3 to 9 μM (Ciavatta et al., 2017).

Onchidione analogues (A–D)

3‐ace​tyl‐1​1‐(3‐​methy​lbuta​noyl)​‐13‐p​ropan​oylil​ikona​pyron​e

Onchidium sp. (4)

Ilikonapyrone esters (E–J)

Onchidium sp. (2) Compound(s) and Activities Anticancer activity: The methanolic extract of this species showed the presence of two cytotoxic, cyclic depsipeptide compounds, viz. onchidin and onchidin B. Both showed anticancer activity against murine P388 leukemia and human KB oral cancer cells with GI50 values of ∼7 μM (Ciavatta et al., 2017).

Compound(s) and Activities Cytotoxicity: This unidentified species produced cytotoxic pyrone-containing propionate and acetate metabolites, peroniatriol I and II. Further additional cytotoxic metabolites identified as the acetates and propionates 1–4 and 6–9 have also been isolated from another identified Onchidium sp. Compounds 1–4 gave the compound onchitriol I, and compounds 6–9 gave the compound onchitriol II (Rodriguez et al., 1991).

        Peroniatriol I             Peroniatriol II

         Onchitriol I             Onchitriol II

Pleurobranchus albiguttatus (Bergh, 1905) Onchidin

Onchidin B

Order: Pleurobranchomorpha  Family: Pleurobranchidae Common name: Mosaic pleurobranch

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Distribution: Western Central Pacific: Philippines and New Caledonia; endemic to southern Africa Ecology: It inhabits coral reefs and lagoon pinnacles at a depth of 5 m; it is nocturnal and hides during the day. Description: This species has a sturdy rounded body with a bumpy skin. Skin has occasional elongated papillae and is a glowing pinkish red. Mantle is patterned with lighter lines, and the margin is lighter than the mantle. There are two rolled rhinophores joined at their bases on the head. Like all other sidegill slugs, there is a single gill on the right-hand side of the body. Animal grows up to 120 mm in total length. Biology Food and feeding: It is carnivorous, feeding exclusively on ascidians. It usually shelters at night, coming out to feed in the daytime. Reproduction: It is a simultaneous hermaphrodite. No other information is available. Compound(s) and Activities Cytotoxicity/antitumor activity: Chlorinated diterpenes such as chlorolissoclimide (1), dichlorolissoclimide (2), and 3β-hydroxychlorolissoclimide (3) have been isolated form this species. While 1 and 2 were potently cytotoxic, with IC50 values 0.7 µM and 1.25 µM, respectively, compound 3 exhibited solid tumor selectivity (Fisch et al., 2017).

 

 

      R=H           R=Cl           R=OH Chlor​oliss​oclim​ide  D​ichlo​rolis​socli​mide ​3β‐hy​droxy​lisso​ climi​de

Pleurobranchus forskalii (Ruppell and Leuckart, 1828)

Order: Pleurobranchomorpha Family: Pleurobranchidae Common name: Forskal’s sidegill slug Distribution: Indo-West Pacific: European waters, Mediterranean Sea, Red Sea

Ecology: P. forskalii is a common nocturnal species. It can occasionally be found in tide pools at moderately exposed rocky sites but is more frequently seen in Halimeda kanaloana beds at depths of 9–10 m. Description: It is a large side-gilled sea slug, oval in outline. Mantle is tough and tuberculate, entirely covering the broad foot, except for the tail, which may just appear posteriorly in active animals. Anterior margin of the mantle is deeply cleft. Rhinophores are curled up to form a tube, united at their bases, with a broad oral veil beneath them. An elongated plumelike gill is present on the right side, between the mantle and the foot. Gill rachis has an alternating double row of tubercles. In adult animals, there is no trace of any internal shell. Body color is very variable, from peach or purple to dark brown or almost black. Opaque white or black circles or polygons are frequently present on the dorsal surface. Foot is of similar color, but slightly lighter. It attains a maximum length of 30 cm. Biology Food and feeding: It is a carnivorous scavenger, feeding on colonal tunicates. Reproduction: It is a simultaneous hermaphrodite whose male and female genitals are jointly functional. The partners will have to mate for a reciprocal exchange of male gametes. Fertilization is internal, and each individual can then lay on its side. The specific patterns of P. forskalii reproduction are not known with certainty. It lays a large, cream, spiral egg mass with a ruffled margin. The development of larvae is not yet well known either (Anon., http:​//dor​is.ff​essm.​fr/Es​peces​/ Pleu​robra​nchus​-fors​kalii​-Pleu​robra​nche-​de-Fo​rskal​-1310​). Compound(s) and Activities Cytotoxicity/antitumor activity: Chlorinated diterpenes such as chlorolissoclimide (1), dichlorolissoclimide (2), and 3β-hydroxychlorolissoclimide (3) have been isolated from this species. While 1 and 2 were potently cytotoxic, with IC50 values 0.7 µM and 1.25 µM, respectively, compound 3 exhibited solid tumor selectivity (Fisch et al., 2017). Blunt et al. (2016) reported that the cyclic dodecapeptide cycloforskamide isolated from this species was mildly cytotoxic.

Cycloforskamide

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Marine Mollusks

Pati et al. (2015) and Fisch et al. (2017) observed that the cyclichexapeptide keenamide A showed cytotoxic/anticancer activity against P 388, A-549, MEL 20, and HT-29 tumor cell lines with GI50 values ranging between 4 and 8 μM.

Keenamide A Ciavatta et al. (2017) and Fisch et al. (2017) reported that the symbiont‐derived, themacrocyclic peptide cycloforskamide of this species showed activity against murine P388 leukemia cells with GI50 value of 5.8 µM. Suarez-Jimenez et al. (2012) reported that this species elicits significant antitumor activity against the P388, A549, MEL-20, and HT-29 tumor cell lines. Neuroprotective effect: The chloroform extract of this species yielded an alkaloid peptide, ergosinine, which is considered medically important because of its significant effect on the central nervous system of humans due to its structural similarity to neurotransmitters (Wakimoto et al., https​://ww​ w.jov​e.com​/visu​a lize​ /abst​ r act/​ 23770​ 424/e​ rgot-​ a lkal​ oid-f​ rom-t​he-se​a-slu​g-ple​urobr​anchu​s-for​skali​i).

Pleurobranchus membranaceus (Montagu, 1815)

Order: Pleurobranchomorpha  Family: Pleurobranchidae Common name: It has no common name. Distribution: Northeast Atlantic and the Mediterranean: United Kingdom and France Ecology: This demersal species occurs mainly in clean rocky areas at depths varying from the surface to 55m. Description: Shell of this species is internal (covered by the mantle), and its length can be up to 50 mm. It is transparent and fragile, and has an aperture so wide that it occupies nearly the whole of the ventral surface. Animal is pale brown, with patches of darker brown on the foot and between the retractile, soft, conical mantle tubercles. Body may reach a maximum length of 12 cm. Biology Behavior: It can swim freely, lying upside down with the mantle hanging down, by undulations of the left and right epipodial lobes. These lobes beat alternately, and the animal rolls on either side of the vertical plane. Food and feeding: It feeds voraciously on compound and solitary ascidians (sea squirts). When it is feeding on a solitary ascidian, a hole is cut at any point in the tunic of the ascidian and the long proboscis is inserted to feed on the tissues within. Reproduction: It lays large and very attractive coils of eggs. No other information is available. Compound(s) and Activities The polypropionate compounds, membrenones A–C, have been isolated from the skin of this species (Jha and Zi-rong, 2004). The pharmaceutical uses of these compounds are however, as yet unknown.

  Ergosinine

   Membrenone A           Membrenone C

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Tylodina perversa (Gmelin, 1791)

Order: Umbraculida Family: Tylodinidae Common name: Yellow tylodina, yellow umbrella slug, yellow umbrella tylodina Distribution: Northeastern Atlantic, including the British Isles and the Mediterranean Sea Ecology: It is a demersal species, inhabiting muddy habitat occurring at the edge of the rocky seabed at a depth of 8 m. Description: This opisthobranch is covered with a conical, limpetlike shell (patelloïde form), which is composed primarily of protein rather than calcium carbonate. Its large enrolled rhinophores have small black eyes at their base. A large gill is found on the right of the body. Adults reach a size of 4 cm. Biology Food and feeding: It is a carnivorous sponge feeder, preferring specimens of Aplysina aerophoba. Reproduction: It is a simultaneous hermaphrodite. The eggs are laid in short ribbons of a few centimeters in length. These spawns can be observed on the sponge A. aerophoba, which is the major food of this species. Compound(s) and Activities Anticancer activity: Among the isoxazoline alkaloids found in this mollusk, isofistularin‐3 displayed anticancer activity against human HeLa cervix carcinoma cells with the GI50 value of ∼9 μM (Ciavatta et al., 2017).

Isofistularin‐3

Bursatella leachii (de Blainville, 1817)

Order: Aplysiida Family: Aplysiidae Common name: Ragged sea hare Distribution: Circumtropical species found nearly worldwide in warm temperate to tropical marine environments Ecology: It occurs in intertidal and subtidal sheltered bay and estuarine habitats with sand or muddy bottoms. It is a frequently encountered component of tropical and subtropical seagrass and mangrove communities. Biology: It is a medium- to large-sized benthic opisthobranch. Body is variably colored, grayish-green to white-tan with dark brown blotches and spots. It is compact and rounded, with distinct head and neck regions. Body is also covered with numerous long, branching fleshy papillae that give the animal its ragged appearance. Gill is covered by a pair of fleshy parapodia. Two long, retractile olfactory tentacles (rhinophores) occur on the head, and two fleshy enrolled oral tentacles also occur at each side of the mouth. Adults completely lack a shell. It is known to secrete purple ink, which is produced from the purple gland, speculated to be a defensive decoy. It grows to a maximum size of 15 cm. Biology Food and feeding: It is a grazing benthic detritivore/herbivore that feeds primarily on cyanophytes and diatom mats and films found on sand, mud, and other benthic substrata. It can also facultatively consume macrophytes such as Ectocarpus and Enteromorpha. Reproduction: As with most sea hares, B. leachii is a crossfertilizing simultaneous hermaphrodite. Ragged sea hares attain sexual maturity at 2–3 months of age and appear to undergo continuous recruitment with no well-defined reproductive season. Fertilization is internal, with one individual transferring sperm via an eversible penis located on the right side of the head to the dorsally located gonopore (genital opening) of a second individual. Inseminated individuals lay large, tangled, spaghettilike benthic egg masses that are usually orange, yellow, green, or brown in color. Growth of the planktonic larvae after hatching is rapid. Veligers attain maximum size approximately 15 days after hatching, and metamorphic competency is reached at 19 days posthatch.

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Compound(s) and Activities Anti-HIV activity: A protein, Bursatellanin P, isolated from the purple fluid of this species has shown anti-HIV activity at the minimum inhibition concentration of 50 mg/ml. This compound, which has a molecular weight of 60 kDa, was stable between pH 5.8 and 8.0. It lost its activity with heating at 60 degrees C for 10 minutes and also with extreme pH values of 2.0 or 10 (Suarez-Jimenez et al., 2012). Anti-inflammatory and cytotoxic activity: The compound malyngamide S isolated from this species has shown antiinflammatory and cytotoxic activity (Gribble, 2010).

Malyngamide S Anticancer activity: The compounds malyngamide S and malyndamide X, both isolated from this species, displayed anticancer activity against seven cancer cell lines, including murine P388 leukemia and human A549 NSCLC, NCI‐H187 (SCLC), HT‐29 colon cancer, HL60 leukemia, KB and BC breast cancer models with GI50 values ranging between ∼4 and ∼8 μM (Appleton et al., 2002).

Aplysia argus (Ruppell and Leuckart, 1830) (=Aplysia angasi)

Order: Aplysiida Family: Aplysiidae Common name: Not designated Distribution: Indo-Pacific: |Ranges from tropical coastline of Australia south to Albany Western Australia and Westernport in Victoria, and including Tasmania Ecology: It frequents seagrass flats, reefs, rocky shelves, and pools and sandy areas to a depth of 15 m. It occasionally enters estuaries. Description: This is a large, dusky gray to light brown sea hare dusted with white flecks and with anastomizing brown lines that may form irregular rings on the sides of the parapodia. Rings appear to become less prominent with increasing age and may be absent in large animals. Edges of the parapodia, rhinophores, and oral tentacles are usually pale violet. It grows to 250 mm in length.

Malyngamide S

Biology Behavior: It is nocturnal and conceals itself under rocks during the day, where it can often be seen in pairs near its egg masses. When disturbed, it ejects bright purple mucous. Food and feeding: These benthic herbivorous creatures graze on various seaweeds. Reproduction: Sea hares are hermaphrodites, with fully functional male and female reproductive organs.

Malyngamide X

Compound(s) and Activities Antileukemic activity: The compound aplysistatin isolated from this species has shown antileukemic activity (Datta et al., 2015).

Cytotoxic, antitubercular, and antimalarial properties: The compound malyngamide X of this species also displayed moderate cytotoxic and antimalarial properties, with ED50 values ranging from 4.1 to 8.2 µM. It also exhibited antitubercular activity with an MIC value of 80 µM (Atta-ur-Rahman, 2012).

Aplysistatin Others: The dibromoditerpene designated angasiol has been isolated from a 2-propanol extract of this species

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(Pereira et al., 2016). The pharmacological properties of this compound are as yet unknown.

Compound(s) and Activities Antitumor, antitypanosomal, antiplasmodial, and antibacterial activities: The compound elatol isolated from this species has been reported to serve as a parasiticide against the amastigotes of Trypanosoma cruzi and Leishmania amazonensis and as a larvicide against the dengue mosquito Aedes aegypti. Further, this compound possesses antitumor and antibacterial activities (Pereira et al., 2016). Anticancer activity: The compound caespitenone of this species was found to be active against HT29, MCF7, and A431 cell lines, exhibiting an IC50 of 18.9, 19.7, and 21.6 µM, respectively (Pereira et al., 2016).

Angasiol

Aplysia dactylomela (Rang, 1828)

Caespitenone The compound thyrsiferol of this species showed a potent and selective activity against P-388 cells, displaying an IC50 of 0.01 µg/mL. It also presented moderate cytotoxicity against A549 and HT29 cells, with an IC50 of 10 µg/mL for both tumor cell lines. Further, in-vitro studies using human breast tumor (T47D) cells showed that thyrsiferol inhibits the activation of hypoxia-inducible factor-1 (HIF-1) (Pereira et al., 2016).

Order: Aplysiida Family: Aplysiidae Common name: Spotted sea hare, black-tailed sea hare Distribution: Worldwide in tropical to warm temperate waters; most commonly encountered in the Indo-Pacific Ecology: It inhabits high subtidal/intertidal zones and shallow waters at 1–2 m depth; sometimes seen near coral reefs. Description: Body of this species is large, fleshy, and smooth; it is more leathery and firmer than other sea hares. Coloration of body is olive green or yellow. It is distinguished by a pattern of black smudged rings, sometimes with white centers, and a network of fine black lines. It has a black “tail.” Inner side of the parapodia is black with striking white blobs. There are two pairs of large tentacles. When disturbed, it releases purple ink. It has a size range of 8–12 cm. Biology Food and feeding: It is an herbivorous species, grazing preferably on green algae. Reproduction: It is hermaphroditic. When mating, one individual acts as a male and crawls onto another one to fertilize it, sometimes forming chains of up to 12 individuals. Eggs form long, tangled strings which may be orange, yellow, green, or brown in color.

Thyrsiferol Antineoplastic activity: Its compound deodactol, an antineoplastic sesquiterpene, was moderately cytotoxic to the L1210 cell line, with an ED50 of 12 µg/mL (Pereira et al., 2016).

Deodactol Cytotoxic activity: The compounds elatol and acetylelatol of this species have shown cytotoxic activity against Vero cells, displaying IC50 values of 25 and 44.6 µM, respectively (Pereira et al., 2016).

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The compound caespitol of this species exhibited very weak cytotoxicity against HeLa 229 cells, presenting an IC50 of 100 µg/mL (Pereira et al., 2016).

Antifungal properties: The compounds elatol and deschloroelatol of this species exhibited some antifungal properties against Mycotypha microspore and Eurotium repens, with deschloroelatol being more active (Pereira et al., 2016).

 

 

  R1=OH R2=C1   R1=OAc R2=C1    R1=OH R2=H      Elatol        Acetylelatol      Deschloroelatol Caespitol Cytotoxicity and antimicrobial activity: The compounds allolaurinterol and isolaurenisol isolated from this species exhibited moderate P388 and BSC-1 cytotoxicity, also revealing significant antibacterial activity against B. subtilis and moderate activity against the fungus T. mentagrophytes (Pereira et al., 2016).

Antiviral activity: The compound nidificene isolated from this species showed antiviral activity against herpes simplex virus-1 (Pereira et al., 2016).

Nidificene Antiviral activity: The compound venustatriol isolated from this species has been reported to possess antiviral activity (Pereira et al., 2016).

        Allolaurinterol            Isolaurenisol Antibacterial activity: Among the compounds isolated from this species, pacifenol together with pacifenediol and pacifidiene exhibited antibacterial activity against the Gramnegative bacteria P. aeruginosa (Pereira et al., 2016).

 

 

     Pacifenol      Pacifenediol       Pacifidiene Its compound, cupalaurenol, exhibited potent inhibition against Staphylococcus sp., Staphylococcus aureus, and Salmonella sp., presenting a minimum inhibitory concentration (MIC) of 125 µg/mL for all strains (Pereira et al., 2016).

Venustatriol Anticancer, antiviral, and antiplasmodial activities: The compound aplysqualenol A of this species exhibited inhibitory activity against SNB-19 central nervous system (CNS) cancer cells and T-47D breast cancer cells, with IC50 values of 0.4 and 0.3 µg/mL, respectively. Further, this compound revealed antiviral properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella zoster virus (VZV), and human cytomegalovirus (HCMV), and remarkable toxicity against Epstein-Barr virus (EBV). Furthermore, aplysqualenols A and B of this species also showed moderate antiplasmodial activity against Plasmodium falciparum, with IC50 values of 11 and 18 µg/mL, respectively (Pereira et al., 2016).

Cupalaurenol Aplysqualenol A

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  Aplysqualenol B Anti-inflammatory activity: The compounds aplysistatin, palisadins A, and 5-acetoxypalisadin B isolated from this species exerted profound inhibitory effects on nitric oxide (NO) production by l LPS-stimulated RAW 264.7 cells. Further, aplysistatin also inhibited prostaglandin-E2 (PGE2) production. This activity has been attributed to the modulation of anti-inflammatory agents via the inhibition of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) expression (Pereira et al., 2016).

       Parguerol               Isoparguerol Further, its dactyloditerpenol acetate revealed a potent capacity to inhibit thromboxane B2 and the superoxide anion generated in LPS-activated rat neonatal microglia, displaying IC50 values of 0.4 and 1 µM, respectively. These results indicate a possible therapeutic approach to ameliorating neuroinflammatory disorders.

Dactyloditerpenol acetate

 

Aplysia depilans (Gmelin, 1791)

         Aplysistatin             Palisadins A

5-acetoxypalisadin B Anti-inflammatory and antibacterial activities: The polybrominated diphenyl ether extracted from this species exhibited potent anti-inflammatory properties and antibacterial activity against E. coli, B. subtilis, and Staphylococcus aureus.

Polybrominated diphenyl ether Neuroprotective properties: The compounds parguerol and isoparguerol of this species induced neurite outgrowth in rat pheochromocytoma PC-12 cells at concentrations of 25 and 50 µM, respectively. These compounds may therefore be of great use in the treatment of various neuronal degenerative disorders.

Order: Aplysiida Family: Aplysiidae Common name: Depilatory sea hare Distribution: Southwest British Isles, Atlantic coast of France to Mediterranean, West Africa Ecology: It is found mostly in shallow water of 1.5–10 m depth. Description: Skin of this species is dark brown to reddish brown, with white to light brown blotches. It has a yellow inner shell that is thinner, flatter, and more poorly calcified than other sea hares and measures about 1.5 cm long. When threatened, these individuals emit a white or purple ink. Individuals can grow up to 40 cm long and weigh up to 380 g. Biology Behavior: A. depilans are one of the seven species of the genus which are known to swim occasionally rather than crawl. Although hermaphrodites, these individuals cannot self-fertilize and require a partner.

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Food and feeding: It feeds mainly on the green alga Caulerpa sp. Reproduction: It is a hermaphrodite, with fully functional male and female reproductive organs. It produces the protein “attractin,” which is a water-borne pheromone that attracts individuals into breeding aggregations and coordinates male and female reproductive behavior within the aggregation.

Aplysia fasciata (Poiret, 1789)

Compound(s) and Activities Anticancer activity: An endoperoxide sterol isolated from the digestive gland of this species showed anticancer activity against human HCT‐116 colorectal cancer cells with a GI50 value of ∼3 μM (Ciavatta et al., 2016). Order: Aplysiida

Family: Aplysiidae

Common name: Mottled sea hare, sooty sea hare, fascial aplasia Distribution: Atlantic coast of France, Mediterranean, West Africa; rare visitor to southern British Isles Endoperoxide sterol Antileishmanial properties: The compound 5α,8αepidioxycholest-6-en-3β-ol isolated from this species showed antileishmanial properties towards amastigote form of Leishmania donovani, with an IC50 of 4.9 µM (Pereira et al., 2016).

5α,8α-epidioxycholest-6-en-3β-ol Others: The methanol extract from the digestive gland of A. depilans showed the presence of health beneficial nutrients such as long-chain polyunsaturated fatty acids (PUFA) and carotenoids, particularly xanthophylls. These constituents could serve as s a good source of nutraceuticals with antiinflammatory potential (Oliveira et al., 2015). The lactonized dihydroxy fatty acids, aplyolides A–E, isolated from the skin of this species could play an important role in reproduction (Spinella et al., 1997). Further activities of these compounds are as yet unknown.

Aplyolides A–E

Ecology: It dwells in tidal and subtidal zones; in gulfs and bays and shallow, calm waters, wherever there is an abundance of algae. Description: Body of this species is globular, soft, and bulky with no outer shell. Body coloration varies from light brown to dark red-brown or red-purple, and there is lighter color mottling on head, neck, and wings. Head has two rounded oral tentacles; smaller rhinophores (tentaclelike sensory receptors) are present behind oral tentacles on neck; and eyes are seen in front of rhinophores. Winglike flaps (called parapodia) are seen on sides of body. Tail is short and rounded. A flap (the mantle) is seen on its back that covers its gills and internal organs; inside the mantle is a very thin, delicate internal shell that is narrow or wide, concave, light amber color, and slightly hooked at apex; also inside the mantle is the ink gland, which secretes purple ink. It grows up to 40 cm. Biology Food and feeding: Like other species of Aplysia, this species feeds upon a wide variety of other algae. In the absence of food, time spent on reproductive behavior increases in this species due to disinhibition of the common arousal. Reproduction: Like all opisthobranch gastropods, fascial aplasia is hermaphrodite and therefore has both sexes simultaneously. Compound(s) and Activities Anticancer activity: The compound 3-epi-aplykurodinone B, a degraded sterol isolated from this species, showed anticancer activity against mouse lymphoma (P-388), human lung carcinoma (A-549), human colon carcinoma (HT-29), and human melanoma (MEL-28) tumor cell lines (ED50 of 2.5 µg/mL in all cases) (Pereira et al., 2016).

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Ecology: It is a benthic species inhabiting coastal waters. Description: Body of this species is dark brownish or purplish-black and is covered with a variable scattering of whitish translucent spots and patches. Parapodia are large and separated posteriorly. It secretes both purple and white ink. It grows to 30 cm in length.

3-epi-aplykurodinone B Anti-inflammatory activity: The lipophilic extract of this species has yielded 25 fatty acids which showed anti-inflammatory properties in RAW 264.7 cells stimulated with lipopolysaccharide, as ascertained by the decreased levels of NO in the culture medium. The EC50 values of NO reduction and lipoxygenase inhibition were found to be 77 µg/mL and 3.1 µg/mL, respectively (Ahmad et al., 2018). Others: The C15-Acetogenins (3Z,9​Z)-7-​chlor​o-6-h​ydrox​ y-12-​oxo-p​entad​eca-3​,9-di​en-1-​yne and (3Z,9​Z,12Z​)-6-a​cetox​ y-7-c​hloro​-pent​adeca​-3,9,​12-tr​ien-1​-yne have also been isolated from this species, with no bioactivity yet described.

(3Z,9​Z)-7-​chlor​o-6-h​ydrox​y-12-​oxo-p​entad​eca-3​,9-di​ en-1-​yne

(3Z,9​Z,12Z​)-6-a​cetox​y-7-c​hloro​-pent​adeca​-3,9,​12-tr​ien-1​-yne

Biology Food and feeding: It feeds on a variety of algal diets. Reproduction: It is a hermaphroditic opisthobranch. In this species, large individuals lay more eggs per brood than small individuals, and there is a strong correlation between animal size and daily egg production. Compound(s) and Activities Anticancer activity: The macrolide compounds aplyronines A–C isolated from this species showed anticancer activity against a human cervical carcinoma cell line (HeLa S3) with IC50 values of 0.45, 2.9, and 22 nM respectively. Further, it has been reported that the treatment with aplyronine A at 1 nM led to potent caspase 3 activation in HeLa S3 cells. Furthermore, aplyronines D–H of this species exhibited cytotoxicity against HeLa S3 cells with IC50 values of 0.075, 0.18, 0.19, 0.12, and 9.8 nM, respectively (Pereira et al., 2016). Antitumor activity: Its compound aplyronine A exhibited exceedingly potent antitumor activity in mouse xenograft models (e.g., P388 murine leukemia, Lewis lung carcinoma, Ehrlich carcinoma, CT26 colon carcinoma, and B16 melanoma) (Pereira et al., 2016).

Aplyronine A

Aplysia kurodai (Baba, 1937)

Order: Aplysiida Family: Aplysiidae Common name: Kuroda’s sea hare Distribution: Western Central Pacific: Philippines; Japan, Korea, China

         Aplyronine B             Aplyronine C

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cells in vitro, displaying IC50 values of 0.28, 1.6 × 10−7 and 0.51 mg/mL, respectively (Pereira et al., 2016).

Aplyronine D Aplaminone

=22- methylaplyronine A Aplyronine E

Neoaplaminone

Neoaplaminone sulphate Aplyronines F–H Anticancer activity: Among the compounds aplysin, debromoaplysin, and aplysinol isolated from this species, aplysin has been reported to act against gastric cancer by inhibiting proliferation and inducing apoptosis of SGC-7901 cells in vitro (Pereira et al., 2016).

 

Further, its compounds aplysiapyranoids A–D exhibited cytotoxicity against epithelial-like monkey kidney Vero cells and Madin-Darby canine kidney (MDCK) and mouse melanoma (B16) cell lines, with IC50 values of 19–96 μg/. Furthermore, its aplysiapyranoid D displayed interesting activity against a human colorectal carcinoma cell line (Moser) (IC50 = 14 μg/mL) (Pereira et al., 2016).

 

  R1=Br R2=H     R1=H R2=H     R1=Br R2=OH    Aplysin      Debromoaplysin      Aplysinol Cytotoxic activity: The prenylated aromatic alkaloid compounds aplaminone, neoaplaminone, and neoaplaminone sulfate of this species were found to be cytotoxic to HeLa S3

Aplysiapyranoids A–D The compound aplaminal of this species also exhibited cytotoxicity against HeLa S3 cells, displaying an IC50 of 0.51 µg/mL (Pereira et al., 2016).

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                R1=H R2=OH       R1=H R2=OAc       Debromolaurinterol  Debromolaurinterol acetate

Aplysia oculifera (Adams and Reeve, 1850)

Aplaminal Another of its compounds, aplysiasecosterol A, exhibited moderate cytotoxicity against the human myelomonocytic leukemia (HL-60) cell line, displaying an IC50 of 16 µM (Pereira et al., 2016).

Aplysiasecosterol A The monoterpene aplysiaterpenoid A of this species showed mild cytotoxicity against various tumor cell lines, displaying IC50 values of 10 μg/mL for mouse lymphoma (L1210), 15.3 μg/mL for human lung carcinoma (QG-90), and 30.2 μg/mL for human breast cancer (MCF-7) (Pereira et al., 2016).

Order: Aplysiida Family: Aplysiidae Common name: Spotted sea hare Distribution: Indo-West Pacific: Maui, Oahu and Midway Ecology: It is an intertidal species, inhabiting sandy sheltered areas among or near seagrasses (Halimeda kanaloana beds) at depths of < 1 to 9 m. Description: This is a brown to olive-green sea hare flecked with white and usually with small white and brown ocelli on the sides of its parapodia. Parapodia are tall and ruffled. Inner surface of the parapodia (wings) has white spots, which form short thin white bars along the edges. It has a size range of 8–10 cm.

Aplysiaterpenoid A

Biology Food and feeding: It feeds on various algal species. This species adapts feeding sequences according to changes in the load and width of food. Reproduction: It is mostly simultaneous hermaphrodite. In this species, the larvae can exist in the plankton and survive for several months until the next recruitment.

Antibacterial and cytotoxic activities: Among the compounds laurinterol, laurinterol acetate, debromolaurinterol, and debromolaurinterol acetate isolated from this species, laurinterol and debromolaurinterol showed more potent antibacterial activity. Moreover, debromolaurinterol, laurinterol, and its acetate showed moderate cytotoxicity against HeLa cells, displaying IC50values of 18, 32 and 20 µg/mL, respectively (Pereira et al., 2016).

Compound(s) and Activities Anticancer activity: Two novel halogenated sesquiterpenes, viz. oculiferane and epi‐obtusane, isolated from the digestive glands of this species displayed anticancer activity against five human cancer cell lines, including the PC‐3 prostate, A549 NSCLC, MCF‐7 breast, HepG2 liver, and HCT116 colon cancer models, with GI50 values ranging between ∼2 and ∼8 μM (Ciavatta et al., 2016).

   

 

         R1=Br R2=OH    R1=Br R2=OAc          Laurinterol       Laurinterol acetate 

            Oculiferane         Epi‐obtusane

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Aplysia punctata (Cuvier, 1803)

Order: Aplysiida Family: Aplysiidae Common name: Spotted sea hare Distribution: Northeast Atlantic from Greenland to Mediterranean; North Sea Ecology: It occurs mainly in very shallow water and occasionally on the lower shore or in rock pools. It is also found on the alga Codium tomentosum. Description: Body color of this species is variable, ranging from olive-green, brown, and red, to purplish-black, with blotches of gray and white, often with black or dark-brown spots and veining. Body is long and narrow, and the parapodia join rather high posteriorly. Penis is broad, spatulate, and devoid of spines. Shell of this species is transparent, fragile, and pale amber in color. It is internal (covered by the mantle) and its size is up to 40 mm in length. Aperture of the shell is wide, occupying nearly the whole of the ventral surface. It grows up to 20 cm. Biology Behavior: If abruptly disturbed, a slimy purple secretion can be emitted by this species. Food and feeding: Like other aplysiids, A. punctata is herbivorous, feeding on various species of algae. Reproduction: Like other species of Aplysia, it is hermaphroditic. In this species, the animals spawn from May, when the sea temperature reaches a minimum of about 9–9.5° C, until about October, with a maximum output of spawn in the late summer, when the animals are fully grown. Compound(s) and Activities Anticancer activity: The compound 5α, 8α-epidioxysterol isolated form this species showed anticancer activity against human colorectal cancer cells (HCT 116), having obtained an IC50 value of 2.5 µM (Pereira et al., 2016).

5α,8α-epidioxysterol

The linear polyhalogenated monoterpenes (1–3) of this species showed identical cytotoxic properties against mice lymphoma (P-388) (ED50 = 2.5 μg/mL), human lung carcinoma (A-549) (ED50 = 1.5 μg/mL), human colon carcinoma (HT-29) (ED50 = 2.5 μg/mL), and human melanoma (MEL28) (ED50 = 1.5 μg/mL) cell lines (Pereira et al., 2016).

             1                       2

                       3 1–3: Polyhalogenated monoterpenes Antileishmanial activity: The compound 5α,8αepidioxycholest-6-en-3β-ol derived from this species exhibited antileishmanial properties, displaying an IC50 of 4.9 µM towards the amastigote form of L. donovani (Pereira et al., 2016).

5α,8α-epidioxycholest-6-en-3β-ol Antibacterial activity: The compound aplysiadiol of this species exhibited a potent effect against Staphylococcus sp., S. aureus, and Salmonella sp. (Pereira et al., 2016).

Anti-inflammatory activity: The lipophilic extract of this species showed the presence of 25 fatty acids with antiinflammatory properties in RAW 264.7 cells stimulated with lipopolysaccharide. It was ascertained by the decreased levels of ˙NO (. EC50 72 µg/mL) and inhibition of lipoxygenase (EC50 1.75 mg/mL) (Ahmad et al., 2018).

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Others: The bioactivity of the compounds epibrasilenol acetate and 6-hydroxy-1-brasilene of this species has not yet been reported (Pereira et al., 2016).

             Epibrasilenol acetate     6-hydroxy-1-brasilene

Dolabella auricularia (Lightfoot, 1786)

Order: Aplysiida Family: Aplysiidae Common name: Wedge sea hare Distribution: Indian Ocean and the western and northwestern Pacific Ecology: This sea hare lives in areas that are sheltered from rough currents and in intertidal rock pools. It often hides in seagrass, sand, and mud, feeding on algae. Description: D. auricularia is a rather large species which can reach a length of 40 cm. Body is wedge-shaped with a small head and a broad, flattened posterior disk. Parapodia are fused except for circular apertures anterior to and in the center of the disk. Surface is intricately tuberculate. Color is highly variable, ranging from dark brown through mottled brown and green to whitish. Biology Behavior: It is nocturnal, concealing itself in crevices or under rocks during the day. When disturbed, it ejects purple dye through the aperture in the center of the posterior disk. Food and feeding: It feeds on a variety of brown, green, and red macroalgae. Reproduction: In this species, spawning and recruitment occur throughout the year, with two peaks: one in May–July, the other in September–October. Egg mass consists of elongate gelatinous filaments laid in tangled masses. Eggs are located within capsules embedded in a gelatinous matrix. Larvae hatch in 9–10 days, with a larval duration of at least 31 days.

Compound(s) and Activities Antileukemic activity: The compound dolatriol isolated from this species has shown antileukemic activity (Datta et al., 2015).

Dolatriol Antibacterial activity: The aqueous ink extracts of this species inhibited the growth of Gram-positive and Gramnegative bacteria (Datta et al., 2015). Antip​rolif​erati​ve/an​tineo​plast​ic/cy​totox​ic/an​tican​cer activity: The depsipeptides dolastatins 10 and 15, small peptides isolated from this species, have shown antineoplastic activity and antiproliferative activity, respectively. Dolastatin 10 inhibits microtubule assembly, causing cells to accumulate in metaphase, and it is extremely potent in vitro. It also caused bone-marrow toxicity in initial clinical trials, as well as local irritation at the injection site and mild peripheral neuropathy. The GI50 index of dolastatin 10 in the NCI 60 cell‐line panel is ∼0.2 nM (Schwartsmann et al., 2001; Suarez-Jimenez et al., 2012).

        Dolastatin 10             Dolastatin 15 Ciavatta et al. (2017) reported that dolastatin 10 displays in-vivo anticancer activity in various models, including, for example, MDR diffuse large cell lymphoma WSU‐DLCL2,214 SCLC NCI‐H446215 and ovarian carcinoma216xenografts. Dolastatin 10 also displayed anticancer activity in various cancer models at the NCI: mouse P388 and L1210 leukemia, B16 melanoma, and M5076 sarcoma as well as human LOX melanoma and MX‐1 breast cancer xenografts. Dolastatin 15 also interacts with tubulin and may bind in the vinca domain of tubulin. Its NCI‐based GI50 is about ten times higher than that of dolastatin 10 (2 vs. 0.2 nM). Dolastatin 1 is most potent anticancer agent discovered, with an 88% life extension (at a dose of 11 μg/kg) in the murine P388 lymphocytic leukemia model and a curative rate (33% at a dose of ∼2 μg/kg) in the murine B16 melanoma model (Ciavatta et al., 2017). Dolastatin 3 displayed the GI50 of 1 μM, respectively. The G150 values of dolastatin 13 and 14 were 14 nM and 20 nM, respectively, in the murine P388 leukemia cell line (Ciavatta et al., 2017). Dolastatin 16’s GI50 values were in low nanomolar ranges when assayed in a mini panel of four human solid cancer cell lines and in five leukemia cell lines. Its mean GI50 in the NCI 60 cell line panel was ∼0.3 μM (Ciavatta et al., 2017). Dolastatin 17’s GI50values were in submicromolar ranges in the four cancer cell lines in which it was assayed; dolastatin 18’s GI50 values were in submicromolar ranges in the mouse P388 lymphocytic leukemia and the human NCI‐H460 NSCLC cell lines; and dolastatin 19 displayed in-vitro growth inhibitory activity with GI50 values of ∼1 μM in breast MCF‐7 and colon KM20L2 cancer cells (Ciavatta et al., 2017). Dolastatin D showed a GI50 value of ∼4 μM in human HeLaS3 cancer cells; dolastatin G and nordolastatin G showed GI50 values of ∼1 and ∼5 μM, respectively, in human HeLaS3 cancer cells; synthetic dolastatin H displayed a GI50 value of 2 nM in human HeLaS3 cancer cells; and isodolastatin H exhibited antitumor activity (Ciavatta et al., 2016).

Dolastatin 14

          Dolastatin 16           Dolastatin 17

           Dolastatin 18             Dolastatin D

Dolastatin G 

            Dolastatin 1              Dolastatin 3

Nordolastatin G

        Dolastatin 11             Dolastatin 12 Dolastatin H

Dolastatin 13 

Isodolastatin H

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The compounds aurilol and auriculol of this species showed cytotoxicity. Aurilol had a GI50 value of ∼7 μM against human HeLa S3 cancer cells (Clavatta et al., 2016). Tringali (2003) reported that this compound showed cytotoxic activity against HeLaS3 cells at 4 µg/mL.

Aurilol Aurilide B

Auriculol Doliculide, a compound of mixed peptides, exhibited marked growth inhibitory effects (GI50 = ∼2 nM) against human HeLaS3 cervix carcinoma cells. It is known to bind with actin and consequently arrests cancer cells at the G2/M phase of the cell cycle by interfering with normal actin assembly (Ciavatta et al., 2017).

Aurilide C

Doliculide

Among the aurisides A and B, auriside A displayed more potent growth inhibitory effects in human HeLaS3 cervix cancer cells than auriside B, and the GI50 values of A and B were ∼ 0.2 μM and ∼2 μM, respectively (Ciavatta et al., 2017).

Aurilide and aurilides B and C, which are cyclic depsipeptides, showed anticancer activity. Aurilide showed antitumor activity and acted against the NCI 60 cell line panel; B and C acted against the NCI 60 cell line panel with a mean GI50 value of ∼0.01 μM, with selectivity towards ovarian, renal, and prostate cancer cell lines. It also displayed marked in-vivo anticancer activity in the NCI hollow fiber assay (Ciavatta et al., 2017).

  

      Auriside A              Auriside B

Aurilide

Auripyrones A and B displayed activity against human HeLaS3 cells with the GI50 of ∼0.5 μM; C‐22 macrolides dolabelide A and its acetyl derivative dolabelide B showed activity against these cells with the GI50 values of ∼8 and ∼2 μM, respectively; and dolabelides C and D showed GI50 values of ∼2 μM (Ciavatta et al., 2017).

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        Auripyrone A             Auripyrone B Soblidotin

Dolabelide A: R1=Ac; R2=H Dolabelide B: R1 =R =H

Marine drugs in clinical trial: The compound derived from this species, namely Pinatuzumab vedotin, which is in in phase I/II (clinical status), targets disease areas such as NonHodgkin lymphoma and leukemia with modes of action viz. apoptosis stimulant, mitosis inhibitor, and tubulin inhibitor. Another compound, Tisotumab Vedotin (HuMax® -TF-ADC) (also in Phase I/II), targets ovarian, endometrium, cervix, and prostate cancer with modes of action such as antineoplastic, drug conjugate, immunotoxin, and monoclonal antibodies (Ruiz-Torres et al., 2017).

Dolabrifera dolabrifera (Rang, 1828) Dolabelide C: R=Ac Dolabelide D: R=H A bisthiazole metabolite, dolabellin, displayed the GI50value of ∼10 μM in the human HeLaS3 cervix carcinoma cell line (Ciavatta et al., 2017).

Dolabellin Medicinal properties: The compounds synthadotin (tasidotin) and soblidotin, synthetic analogs of dolastatin isolated from this species, have been reported to possess medicinal properties, which are in trial (Datta et al., 2015).

Synthadotin

Order: Aplysiida Family: Aplysiidae Common name: Warty seacat Distribution: Worldwide in tropical and subtropical seas and oceans Ecology: It is found in the low intertidal and tide pools in rocky areas; occurs at protected to exposed locations; depth range 0–16 m. Description: It is a relatively small flattened sea hare which grows to about 11 cm in length. It is usually a mottled green or light brown but ranges in color from pink to dark brown. Posterior half of the animal is usually broad and rounded, gradually narrowing anteriorly to the head. Parapodia are fused except for a short region in the posterior midline, where two small flaps form, and an inhalent and exhalent opening into the parapodial chamber, which encloses the reduced mantle cavity and shell. Body is covered in lower tubercles which bear retractile single or compound papillae. Biology Food and feeding: It feeds primarily on seaweeds. Reproduction: This nocturnal sea hare lays egg masses composed of a flattened egg string attached to the bottom of a rock in a tight, zig-zag pattern.

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Compound(s) and Activities Antileishmanial activity: The compound 5α,8αepidioxycholest-6-en-3β-ol isolated from this species showed antileishmanial activity. It was mildly active against the amastigote form, with nearly sixty-fold selectivity versus Vero cells (Blunt et al., 2016).

5α,8α-epidioxycholest-6-en-3β-ol

Stylocheilus longicauda (Quoy and Gaimard, 1824) (=Stylocheilus citrina)

Order: Aplysiida Family: Aplysiidae Common name: Long-tailed sea hare, longtail seacat Distribution: Indo-Pacific: South Africa: Mascarenes to Japan across to the Sea of Cortez, Mexico. Western Atlantic. Ecology: It is a benthic species found in sheltered pools and estuaries; also found on floating algae; crawls around rocky areas and walls with good algae coverage; depth range 2–8 m. Description: Body of the animal is elongated. Dorsal color of the animal is bright yellowish-green with blue spots circled with orange-red. Ventral side of the animal is pale yellow in color. Several small papillae are found scattered on the dorsal surface, and a few larger branched papillae are present around the genital opening. Tail of the animal is long, slender (nearly half of total length), and almost ribbonlike in structure. A pair of tubular, elongated, oral tentacles and rhinophores are present above the head. Clearly visible penis (white half-moon structure) is observed on the right side of the head. Parapodia are equal, small in size and shape, and lightly fastened. Skin has simple and compound villi. Shell is absent;

foot is moderately broad and is prolonged posteriorly as a slender tail. It attains a maximum length of 7.5 cm. Biology Food and feeding: It is a specialist grazer on the toxic cyanobacterium (blue-green alga) Lyngbya majuscula. Reproduction: This species develops planktotrophically and has a ≈ 30-day larval phase. The larval phase includes a period of rapid shell growth to a species-specific size, followed by a nongrowth period during which other morphological developments occur to culminate in metamorphic competence. The larvae metamorphose preferentially on a particular species of benthic algae. The events of metamorphosis require 2–4 days for completion and transform the planktonic filter-feeding larva into a benthic, radular-feeding juvenile. Postlarval development includes growth of the shell, parapodia, oral tentacles, rhinophores, anal siphon, and structures of the mantle cavity (Switzer-Dunlap and Hadfield, 1977). Compound(s) and Activities Antitumor activity: The feed-derived compound aplysiatoxin of this species, which is a potent irritant and carcinogen, acts as a powerful activator of protein kinase C. While this action has a tumor-promoting effect, protein kinase C activation can be medically beneficial for some other applications, and synthetic analogues of aplysiatoxin have been researched for anticancer effects (Wikipedia).

Aplysiatoxin Blunt et al. (2016) reported that the synthetic, debromo analogs of aplysiatoxin may play a role in the antiproliferative activity. The cyanobacterial feed-derived cyclic bidepsipeptides, kulokekahilide‐1 and kulokekahilide‐2, of this species show cytotoxic activity (Ciavatta et al., 2017).

Kulokekahilide 1

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Kkulokekahilide 2

        Lyngbyatoxin A     Lyngbyatoxin A acetate

Tambja ceutae (Garcia-Gomez and Ortea, 1988)

Malyngamide O The chlorinated metabolites makalika ester and makalikone ester isolated from this species showed moderate activity against the cancer cell lines P388, A549, and HTB38, with IC50 values in the range of 2.5–5 µg/mL (Fisch et al., 2017).

        Makalika ester          Makalikone ester

Stylocheilus sp. Compound(s) and Activities Anticancer activity: The feed-derived compounds of this species are lyngbyatoxin A and lyngbyatoxin A acetate. Of these, the lyngbyatoxin A acetate showed very potent toxicity against cancer cell lines tested with an IC50 value of 0.05 µg/mL (Fisch et al., 2017).

Order: Nudibranchia Family: Polyceridae Common name: Not designated Distribution: Mediterranean Sea. Ecology: It is a benthic species inhabiting the roof of underwater caves at a depth of 1 m. Description: Head of this species is widened and has seven prominences on the edge of the noto; another six similar bulges are observed on the left side, and five on the right. On the back of the caudal region can also be seen another six bulges. There are short oral tentacles. Rhinophores have 20 lamellae and a split apex. Five gills, which are tripinnate and nonretractable, surround the anal papilla, the first three of these being more developed. Background color is dark blue-green. Edge of the noto has a yellow band which is interrupted in the back. A yellow line emerges from the middle edge area of the cephalic noto and continues through the middle of the animal’s back. It attains a size of 35 mm. Biology Food and feeding: It has been reported to feed on the green, arborescent ectoproct Bugula dentata. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into the (planktonic) vestigial veliger larval stage before further development into adults. Compound(s) and Activities Anticancer activity: The alkaloid compound tambjamine K isolated from this species displayed activity against four cancer cell lines with GI50 values ranging from ∼0.004 and 15 μM. This compound showed a GI50 value of ∼19 μM with

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mouse 3T3‐L1 fibroblasts. Further, it displayed a ∼4000‐fold differential sensitivity between human Caco‐2 colon cancer cells and HeLa cervical cancer cells. Tambjamine K therefore certainly merits additional in-depth pharmacological and toxicological preclinical evaluations as a potential anticancer agent (Ciavatta et al., 2017).

Tambjamine K Carbone et al. (2010) reported on the occurrence of tambjamine K and minor tambjamines A and B (isolated as a mixture from the extract) from this species. Tambjamine K showed cytotoxicity against HeLa cells, C6 cells, H9c2 cells, and 3T3-L1 cells with IC50 values of 14.6, 14, 2.7, and 19 µM, respectively. This compound also exhibited activity against CaCo-2 cells. The pharmaceutical role of tambjamines A and B is as yet unknown.

Biology: The background color varies from yellow-ocher to a darkish brown-gray. It usually features a series of longitudinal turquoise blue bands margined with a thin black line, but in specimens from Costa Rica, the turquoise bands are broken into a series of elongate spots which are joined, like a string of beads, by a continuation of the black line that borders the spots. The gills are black with a blue line along the inside edge of the rachis. The outside edge of the rachis is khaki or yellow-ocher at base and blue at tips. Maximum length is 8.0 cm. Biology Food and feeding: It feeds on the bryozoan Sessibugula translucens. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage, before developing into adults. Compound(s) and Activities Cytotoxic and genotoxic effects: The compound tambjamine D isolated from this species displayed a potent cytotoxic effect in V79 cells with an IC50 value of 1.2 microg/mL. This compound increased the number of apoptotic cells in a concentration-dependent manner at all concentrations (0.6, 1.2, 2.4 and 4.8 microg/mL) tested. Tambjamine D also induced DNA strand breaks and increased the micronucleus cell frequency at all concentrations evaluated, showing a genotoxic risk induced by tambjamine D (Cavalcanti et al., 2008).

             R=H                  R=Br        Tambjamine A          Tambjamine B

Tambja eliora (Marcus and Marcus, 1967)

Order: Nudibranchia Family: Polyceridae Common name: Blue-striped sea slug Distribution: Eastern Pacific; Gulf of California; Costa Rica and Ecuador Ecology: It is a demersal species.

Tambjamine D

Tyrannodoris tigris (Farmer, 1978) (=Roboastra tigris)

Order: Nudibranchia Common name: Tiger doris

Family: Polyceridae

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Distribution: Eastern Central Pacific: Mexico; Gulf of California Ecology: It is a benthic species with a depth range of 5–70 m. Description: It can grow as large as 30 cm in length. Biology Food and feeding: Like other nudibranchs in the genus Roboastra, it is carnivorous and predatory, feeding on other sea slugs. It grasps the prey with its radular teeth and swallows it whole. It is reported to feed on the bryozoan-feeding nudibranchs Tambja eliora and Tambja abdere and is also cannibalistic, eating others of its own kind. Reproduction: Not reported. Compound(s) and Activities The methoxypyrrolic alkaloids tambjamines A–D have been isolated from this species. The pharmaceutical activities of these compounds are, however, as yet unknown (Ciavatta et al., 2017).

        Tambjamine A            Tambjamine B

Distribution: Indo-West Pacific: Red Sea, Tanzania, Japan, New Caledonia, and eastern Australia; Mauritius, Mayotte, and Madagascar Islands Ecology: It is found most often at night on soft corals on the seaward reef; also under rocks near soft coral colonies on the seaward reef and on lagoon reefs and pinnacles. Description: It is a slender nudibranch growing to about 5 cm, with several pairs of dendritic (branching) cerata and rhinophores tipped with short tentacles. It varies in color from translucent clear to translucent orange or orange-red and has a pattern of white opaque markings. Both color forms can be found together on the same colony of soft coral. It has a normal size range of 15–20 mm. Biology Food and feeding: It is a predator feeding on corals Lobophyton sp., Carijoa riisei, Sarcothelia edmonsoni, and Sinularia densa. Reproduction: Not reported. Compound(s) and Activities Anticancer activity: The compound tritoniopsin A isolated from this species showed weak to moderate cytotoxicity against a selection of rat cell lines (Dean and Prinsep, 2017). Ciavatta et al. (2011) reported on the occurrence of four diterpenes, tritoniopsins A-D. Among these compounds, tritoniopsin B exhibited antiproliferative activity against tumor cell lines.

       Tambjamine C            Tambjamine D Tritoniopsin A

Tritoniopsis elegans (Audouin, 1826) (=Tritoniopsilla alba)

Order: Nudibranchia Family: Tritoniidae Common name: Splendid sea slug

Tochuina tetraquetra (Pallas, 1788)

Order: Nudibranchia Family: Tritoniidae Common name: Giant orange tochui Distribution: North Pacific from Northern Japan, Kuril Islands (Russia), Alaska, Canada, and south to California Ecology: It lives on rocks from subtidal to a depth of 363 m.

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Description: It is one of the largest nudibranchs. It has a large, stout body with white, plumose gill tufts along the undulating dorsolateral margin all the way from the rhinophores to the posterior tip. Anterior border of the oral veil is white and crenulate but does not have papillae. Dorsum is orange or yellowish-orange with white-tipped tubercles. Foot is salmon pink to yellow with a white margin. Rhinophores have six to ten short, vertical plumose processes encircling the main shaft below the tip. It attains a maximum length of 30 cm and weight of 1.4 kg.

Marionia limceana (Silva, de Meirelles, and Matthews-Cascon, 2013)

Biology Food and feeding: It feeds on octocorals, including sea pens, gorgonians, and soft corals. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage and then developing further as adults. Compound(s) and Activities Terpenoid metabolites such as tochuinyl acetate, dihydrotochuinyl acetate, rubifolide, ptilosarcenone, butanoate analogue of ptilosarcenone, and ptilosarcone have been isolated from the skin extracts of this species. The pharmaceutical activities of these compounds are, however, as yet unknown (Williams and Aandersen, 1987; Blunt et al., 2006).

            1          2 

                 3                     4

Order: Nudibranchia Family: Tritoniidae Common name: Not reported Distribution: Off northeast Brazil Ecology: It is an intertidal species. Description: This species has the following characteristics: branched papillae in the veil, a sturdy white body of which the notum is covered with two rows of red polygons running from the rhinophores to the tail, separate digestive glands, 18 hard stomach plates, 11–14 pairs of gills, and a jaw with three to four rows of denticles on the inner lips. It grows up to 3.1 cm in length. Biology Food and feeding: Stragulum bicolor (octocoral) is the main component of the diet of this new species. Reproduction: Not reported as it is a new species. Compound(s) and Activities Cytotoxicity: The macrolactone amphidinolide P isolated from the methanol extract of this species showed moderate cytotoxicity against the colon adenocarcinoma cell line HCT-116 with an IC50 of 47.20 μg/ml (Dean and Prinsep, 2017).

            5,6                      7 1, Tochuinyl acetate; 2, Dihydrotochuinyl acetate; 3, Rubifolide; 4, Pukalide; 5, Ptilosarcenone; 6, butanoate analogue of ptilosarcenone; 7, Ptilosarcone

Amphidinolide P

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Phidiana militaris (Alder and Hancock, 1864)

Order: Nudibranchia Family: Aeolidiidae Common name: Military phidiana Distribution: Tropical Indo-West Pacific Ecology: It is a benthic species inhabiting shallow water, mangroves, rocky habitats, and reefs. Description: This species is characterized by the brightorange median line on the head, which forks anteriorly, with a branch running up the anterior edge of each oral tentacle. Another orange line runs along the posterior edge of each oral tentacle and then runs along each side of the body below the cerata. Oral tentacles, rhinophores, tentacular foot corners, and cerata are all tipped with yellow, and there is a broad orange band on the rhinophores. It attains a maximum length of 3 cm. Biology Food and feeding: It feeds mainly on hydroids. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Anticancer activity: The indole alkaloids phidianidines A and B isolated from this species showed activity against three cancer cell lines, with GI50 values ranging between ∼0.4 and >100 μM. Phidianidines A and B act as selective and potent ligands with partial agonist activity against the μ opiod receptor (versus δ‐ and κ‐opiod receptors) (Ciavatta et al., 2017).

Phidianidine A; R=Br Phidianidine B; R=H

Peltodoris atromaculata (Bergh, 1880) (=Discodoris atromaculata)

Order: Nudibranchia Family: Dorididae Common name: Dotted sea-slug, leopard sea slug Distribution: Mediterranean and nearby Atlantic coasts Ecology: It lives in dark and shady underwater areas, in caves on the walls or ceiling, and can be found at any depth. It is usually found on the stony sponge Petrosia ficiformis. Description: It has an oval body and is easily recognized by its dark brown spots on a white background. These spots are distributed randomly, although the larger and darker ones are generally located on the central portion of the body of the animal. When the animal is resting, the outline of its body is nearly circular and hard to the touch. It has featherlike gills on the rear part of the body. It has eight appendages on three branches. It also has two rhinophores on the front part of the body. These rhinophores are olfactory organs comprising 25 lamellae. Rhinophores and gills are white. It can grow to approximately 120 mm in length. Biology Food and feeding: It feeds exclusively on the sponge Petrosia ficiformis. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Anticancer activity: The sponge-derived secondary metabolites extracted from the digestive glands of this species, viz. petroformynes, exhibited in-vitro growth inhibitory effects against cancer cells, with GI50 values ranging between 0.1 and 0.7 μM in murine P388 leukemia cells. Further, a new polyacetylene, viz. hydroxyl‐dehydroisofulvinol, isolated from this species displayed a GI50 value of ∼3 μM against SKMEL28 melanoma cells(Ciavatta et al., 2017).

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cardiovascular effects, including slowing down of the heart and hypotension, in mice and guinea pigs (Cimino et al., 1986).

Hydroxyl‐dehydroisofulvinol

Peltodoris nobilis (MacFarland, 1905) (=Anisodoris nobilis; Montereina nobilis)

1-methylisoguanosine(doridosine) Cardiovascular effects: The bioactive nucleoside characterized as 1-methylisoguanosine (doridosine) isolated from the organic extracts of this species showed skeletal muscle relaxant, hypothermic, and cardiovascular effects mediated via adenosine A1 and A2 receptors (Datta et al., 2015; García et al., 2018).

Order: Nudibranchia Family: Dorididae Common name: Sea lemon, false sea lemon, noble dorid Distribution: West Coast of North America from Alaska to Baja California, Mexico Ecology: It is found on exposed/protected rocky shores and kelp forests; lives both intertidally and subtidally to depths of 250 m. Description: This nudibranch is variable in color, from a very pale yellow through a rich yellow to a rather dark orange. Gill rosette is tinged with white at the tips. Dorsum is covered in tubercles. There are a number of dark spots on the dorsum. These dark spots vary widely in number from one individual to the next. This animal can grow to be as large as 200 mm.

Doris fontainii (d’Orbigny, 1837) (=Anisodoris fontaini)

Order: Nudibranchia Family: Dorididae Common name: Peruvian dorid, Patagonian dorid Distribution: Pacific and Atlantic coasts of southern South Biology America from northern Argentina to southern Peru Food and feeding: This species does not have a radula, yet it feeds on several species of sponges. Its favorite prey is the Ecology: This benthic species is found on rocky substrates breadcrumb sponge, Halichondria panicea. Its color often and stones from the intertidal area to a depth of 100 m. matches the color of the sponge it eats. The animal first mac- Description: Mantle of this species is highly arched and coverates its food and then sucks out soft tissue. ered in large rounded tubercles, which can reach 5 mm or Reproduction: A sea lemon, like all nudibranchs, can pro- more in diameter in the midregion but are somewhat smaller duce both sperm and eggs (it is hermaphroditic), who mutu- towards the edge. Body ranges in color from yellow or yellowally copulate. Females lay circular, elaborate, light yellow orange to brownish, and the space between the tubercles often ribbons containing as many as 2,000,000 eggs. The ribbon is forms a network of brown. Sometimes the center of large attached in a coil by one edge to a hard substrate. Eggs hatch tubercles is darker colored than the rest of the tubercle. There in 20–25 days, and trochophore larvae settle within about 2 are five to seven large tripinnate gills, and the oral tentacles hours of hatching. In Monterey Bay, the typical spawning sea- are flattened and triangular with a groove along the outer son is from November to March (Anon., https​://sa​nctua​rysim​ edge. Front of the foot is bilabiate, that is, split into upper and on.or​g /dbt​ools/​speci​es-da​t abas​e/id/​832/m​onter​eina/​nobil​is/ lower flaps, but the upper flap is not notched. This species no​ble-s​ea-le​mon).​ grows to at least 118 mm long and 65 mm wide. Compound(s) and Activities Antihypertension activity: The compound 1-methylisoguanosine isolated from the organic extract of this species produced

Biology Food and feeding: It feeds on brownish encrusting demosponges.

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Reproduction: Spawning is observed during southern summer and autumn. Egg mass is a very long yellowish ribbon forming a spiral with up to seven whorls. There are three to four small spherical eggs in each capsule. Compound(s) and Activities Compounds: Diterpenoid diacylglycerols such as anisodorins 1−5 have been isolated from the mantle of this species. The functions of these compounds however, are as yet unknown (Gavagnin et al., 1999).

          Anisodorin 1               Anisodorin 2

Distribution: Sub-Antarctic and Antarctic waters; Southeast Pacific, Southwest Atlantic, and the Antarctic; Weddell & Ross Seas, Kerguelen Islands, and the southern tip of South America Ecology: It is a benthic, polar species; depth range 0–786 m. Biology: A. kerguelenensis ranges in color from white to bright yellow. It attains a maximum length of 12 cm. Biology Food and feeding: It feeds mainly on rossellid, glass sponges. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Anticancer activity: The compounds isolated from this species include clerodane, labdane, and halimane diterpene glyceride esters, named palmadorins. Palmadorins A, B, D, M, N, and O inhibited human erythroleukemia (HEL) cell proliferation with low micromolar GI50values, while palmadorin M inhibited JAK2, STAT5, and Erk1/2 activation in HEL cells and caused apoptosis at 5 μM (Ciavatta et al., 2017; Diyabalanage et al., 2010).

      Anisodorin 3            Anisodorin 4

         Palmadorin A            Palmadorin B

  Anisodorin 5

Doris kerguelenensis (Bergh, 1884) (=Austrodoris kerguelenensis)

          Palmadorin C            R1=H; R2=H; R3=H;R4=CH2OH                   Palmadorin D

     Order: Nudibranchia Family: Dorididae Common name: Not designated

    Palmadorin M        R1=H; R2=CH2OH; R3=CH2                               Palmadorin N

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Archidoris montereyensis (Cooper, 1862)

Palmadorin O Compounds: This species has also skin secondary metabolites, viz. ent-labdane diterpenoid glycerol; alimane diterpenoid glycerol, austrodorins; 1,3-glyceryl esters; 1,3-glyceryl ester derivatives; austrodorins A; austrodorins B; and (S) – and (R)- esters. The activities of these compounds are, however, as yet unknown (Gavagnin et al., 2000).

1

         2,3,5,9,10,11                 4,6,12,13

             7                         8 1: ent-labdane diterpenoid glycerol; 2: alimane diterpenoid glycerol, austrodorins; 3,4: 1,3-glyceryl esters; 5,6: 1,3-glyceryl ester derivatives; 7: austrodorins A; 8: austrodorins B; 9: 10,11: (S) – and (R)- esters; 12,13: (S) – and (R)- esters.

Order: Nudibranchia Family: Dorididae Common name: (False) sea lemon, Monterey dorid, Monterey sea-lemon Distribution: Alaska to San Diego; California Ecology: It is an intertidal species found at depths of up to 50 m; rocky areas and pilings; open coast and protected waters. Description: This large dorid nudibranch is primarily a solitary animal. It has an anus on the dorsal midline about a quarter of the length from the posterior end. Its seven gills can be completely retracted. Perfoliate rhinophores are stout at the base and taper from base to tip. Dorsum has prominent tubercles. Body coloration is lemon yellow with darker rhinophores and gills. There are black spots on the dorsum, on and between tubercles. Number of spots per individual seems to vary quite a lot, and some have only a few spots. It grows up to 15 cm. Biology Food and feeding: The sea lemon primarily feeds on encrusted sponges, especially Halichondria spp. and Haliclona spp. It uses its radula to scrap the sponge off the substrate and then ingest it. Reproduction: Animals are simultaneous hermaphrodites. They lay their eggs throughout the year. Nonmotile sperm from a partner is stored in a seminal receptacle for some time before the sperm become motile and fertilize the eggs as they are laid. Eggs are in capsules of several eggs each, which are then formed into a narrow cord which is folded into a bright yellow or cream gelatinous ribbon of about 2 million eggs. Eggs hatch in 20–25 days, and trochophore larvae settle within about 2 hours of hatching. Compound(s) and Activities Antibacterial activity: The compound hexadecyl-glycerol isolated from this species showed antibacterial activity in vitro against Staphylococcus aureus and B. subtilis (Datta et al., 2015).

Hexadecyl-glycerol

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Marine Mollusks

Jorunna funebris (Kelaart, 1858)

          Jorumycin            Jorunnamycin A

Order: Nudibranchia Family: Dorididae Common name: Dotted nudibranch, polka-dot nudibranch, Sunday nudibranch. Distribution: Tropical Indo-West Pacific; Sri Lanka; from the Red Sea and the Indian Ocean along the East African coast to Australia and New Caledonia Ecology: It lives in seagrass meadows, coral rubble, and coral reefs; depth range 10–21 m. Description: Animals of this species have a fleshy oval body and are white with black circular markings. These markings are actually made up of tiny raised black bristles on the skin (called caryophyllidia). Entire body may also be covered with white bristles, giving the animal a fuzzy appearance. It has black-tipped rhinophores and black edging on feathery gills on the back. Size of the animal ranges from 1 to 6 cm. Biology Food and feeding: It is a carnivore, feeding on sponges such as Xestospongia sp., Haliclona sp., Euplacella cf. australis, and Oceanapia sp. Reproduction: It is a simultaneous hermaphrodite. It lays a ribbonlike egg mass on a substratum where the eggs develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Antitumor activity: The compound jorumycin isolated from the mantle and mucus of this species showed anticancer activity against cancer cell lines P388, A549, HT29, and MEL28 with IC50 = 12.5 ng/mL (Fisch et al., 2017). Mayer and Gustafson (2003) reported that this compound showed antitumor activity against human and murine tumor cell lines. The tetrahydroisoquinoline alkaloids jorunnamycins A–C have been isolated from the mantle, viscera, and egg‐ribbons of this species. While the activities of jorunnamycins A and B are not known, jorunnamycin C of this species acted against human colon (HCT‐116) and breast (MDA‐MB‐435) cancer cells with GI50 values in the low nanomolar ranges (Ciavatta et al., 2017).

       Jorunnamycin B         Jorunnamycin C Zalypsis® (PM00104/50) is PharmaMar’s fifth new marinederived compound that has begun Phase I clinical trials for the treatment of solid tumors. Zalypsis® is a novel chemical entity related to the jorunnamycin. Zalypsis demonstrated strong in-vitro and in-vivo antitumoral/cytotoxic activity in a wide variety of solid and hematological tumor cell lines and human transplantable breast, gastric, prostate, and renal xenografted tumors. Zalypsis also demonstrated a manageable and reversible preclinical toxicology profile (Fontana et al., 2000).

Glossodoris rufomarginata (Bergh, 1890) (=Chromodoris youngbleuthi)

Order: Nudibranchia Family: Chromodorididae Common name: White-margin sea slug, caramel nudibranch Distribution: Tropical Indo-West Pacific Ecology: It is mostly found on reefs and rocky areas in sheltered, exposed environments, but with a preference for areas in the shade. Description: Background coloration of the entire body is whitish with on the foot and the dorsal surface, speckled with a dense coat of tiny red to orange-brown dots. Edge of

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the mantle is well developed and wavy with a broad white band with a red to orange-brown outer border. Foot has also a white external margin. Rhinophores and branchial plume are retractable, showing a red to orange-brown coloration with a white median line on rhinophores and a white highlight on the gills axes. It attains a maximum length of 5 cm. Biology Food and feeding: They feed mainly on gray sponge (Cacospongia sp.). Reproduction: They are simultaneous hermaphrodites, and mating takes place by darting. The individual who darts the other first becomes the dominant male and the other the female. Eggs are laid on a solid substrate. The foot is used to manipulate the egg ribbon and help in the process of fastening it to the rock in a spiral. When they hatch, the larvae become planktonic before growing into adults. Compound(s) and Activities Cytotoxic, antitumor, and anti-inflammatory effects: The diet-derived scalaradial of this species showed cytotoxic, antitumor, and anti-inflammatory effects. It showed strong antitumor activity against several human cancer cell lines (leukemia HL60, IC50 = 3.4 μM; hepatocarcinoma BEL7402, IC50 = 5.8 μM; breast cancer MDA-MB435, IC50 = 4.8 μM). Scalaradial also exhibited potent activity against phospholipase A2 (PLA2) enzymes, which are involved in the biosynthesis of eicosanoids responsible for the inflammatory response. Thus, scalaradial (2) was found to inhibit PLA2 from bee venom (IC50 = 0.07 μM and human recombinant PLA2 (IC50 = 0.07 μM) (González, 2010).

R1=α-OAc; R2=β-CHO Scalaradial Cytotoxic activity: The compound desacetylscalaradial of this species showed cytotoxic activity against L1210 cancer cells (IC50 = 0.58 μg/mL) (González, 2010).

Desacetylscalaradial

Antitubercular, cytotoxic, and antimicrobial activities: The diet-derived compound of this species, 12-Deacetyl-12-episcalaradial, displayed both antitubercular (MIC = 64 μM) and cytotoxic activity (ovarian cancer SKOV3, IC50 = 31.0 μM; melanoma SK-MEL, IC50 = 26.4 μM; breast cancer BT549, IC50 = 19.4 μM; Vero, IC50 = 19.4 μM), as well as antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 22 μM (González, 2010).

12-deacetyl-12-epi-scalaradial The compound 12-Deacetyl-12-oxoscalaradial of this species displayed both antitubercular (MIC = 130 μM) and cytotoxic activities (ovarian cancer SKOV3, IC50  =  41.6 μM; melanoma SK-MEL, IC50 = 14.6 μM; breast cancer BT549, IC50 = 15.6 μM; Vero, IC50 = 18.2 μM), as well as antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 27.8 μM (González, 2010).

R1==O; R2=β-CHO 12-Deacetyl-12-oxoscalaradial Cytotoxic and antimicrobial activities: The compound 12-Deacetyl-18-epi-12-oxoscalaradial of this species displayed cytotoxic activity (ovarian cancer SKOV3, IC50 = 31.2 μM; melanoma SK-MEL, IC50 = 14.3 μM; breast cancer BT549, IC50 = 15.6 μM; Vero, IC50 = 15.6 μM), as well as antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 30.1 μM (González, 2010).

R1==O; R2=α-CHO 12-Deacetyl-18-epi-12-oxoscalaradial

147

Marine Mollusks

Goniobranchus cavae (Eliot, 1904) (=Chromodoris cavae)

         Chromodorolide-A       Chromodorolide-B

Goniobranchus obsoletus (Rüppell and Leuckart, 1830) (=Chromodoris obsoleta) Order: Nudibranchia Family: Chromodorididae Common name: Not reported Distribution: Zanzibar and Tanzania; northeast coast of South Africa, Réunion, Mauritius, and India Ecology: It lives in subtropical tidal reefs, rocky reefs, seagrass, and artificial reefs. Description: Color of the animal is yellowish white, with indefinite large drab blotches laterally. Edges of mantle and foot are bordered with light violet. On the back are black spots surrounded by a white line and also irregular dull orange spots. Foot is not very broad and is white in color, with a row of dull orange spots and black spots below them. Tip and anterior side of the rhinophores are purple, and lamellae are reduced to fine striations. It attains a size of 4.2 cm. Biology Food and feeding: It feeds mainly on sponges. Reproduction: Chromodoris is an hermaphrodite, and animals reproduce at all times of the year. Compound(s) and Activities Antimicrobial, cytotoxic, and nematocidal activities: The chromodorane diterpenes chromodorolides A and B have been isolated from this species. Chromodorolide A has been reported to exhibit cytotoxic and antimicrobial activity. When tested individually against the P388 cell line, chromodorolides A and B displayed significant inhibition (66% and 70% respectively) at concentrations of 10 μg/ mL. Chromodorolide A also showed nematocidal activity against the larval stages of Haemonchus contortus and Trichostrongylus colubriformis, two important pathogens of sheep and other ruminants. A concentration of 100 μg/ mL caused 94% and 95% inhibition of the development of H. contortus and T. colubriformis larvae, respectively. A concentration of 10 μg/mL affected the development of H. contortus with 33% (Rungprom et al., 2004; Kiran et al., 2014).

Order: Nudibranchia Family: Chromodorididae Common name: Obsolete chromodoris Distribution: Western Indian Ocean: Red Sea, Persian Gulf, and Arabian Sea Ecology: This benthic species seems to climb on leaf kelp; depth range 5–15 m. Description: G. obsoletus has a mostly white mantle and an orange mantle edge. There is an irregular band of blue-black just inside the orange margin, and the mantle is rugose with an orange-brown reticulation between the raised pustules. Rhinophores and gills are translucent brown with white markings. It attains a maximum length of only 1.5 cm. Biology Food and feeding: It feeds primarily on sponges. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before further developing as adults. Compound(s) and Activities Anticancer activity: A series of dorisenones and related spongian diterpenoids isolated from this species recorded GI50 values ranging between submicromolar and low micromolar in mouse L1210 leukemia and human KB cells (Ciavatta et al., 2016). Fisch et al. (2017) reported that dorisenones A, B, D, 11β-hydroxyspongi-12-en-16-one, and spongian-16-one of this

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species were found to exhibit cytotoxicity as low as IC50 = 0.2 µg/mL against murine lymphoma LI210 and human epidermoid carcinoma KB cells.

  

Goniobranchus splendidus (Angas, 1864)[1]

    

                R=OH Dorisenone A; R=OAc; R1=OH        11β-hydroxyspongi-12-en-16-one Dorisenone B; R=H; R1=OH Dorisenone D; R=OAc; R1=H

Spongian-16-one Cytotoxic activity: The compound dorisenone C of this species showed cytoxicity (González, 2010).

Order: Nudibranchia Family: Chromodorididae Common name: Splendid nudibranch Distribution: Endemic to New South Wales and southern Queensland; Solitary Islands Marine Park Ecology: It lives on walls and rocky reefs to a depth of 25 m. Description: It has an opaque white mantle with large, scattered red spots, which coalesce and may form a single large red patch in the middle of the back. Edge of the mantle is yellow. Rhinophore clubs are red with white edges to the lamellae. Gills have a two fine red lines on the outer rachis and white leaves. Its normal size is 3 cm. Biology Food and feeding: It feeds primarily on sponges. Reproduction: Not reported. Compound(s) and Activities Cytotoxic activity: The compound epoxygoniolide-1 isolated from this species showed moderate cytotoxicity to NCIH460, SW60, or HepG2 cancer cells (Forster et al., 2017).

Δ 13 R=Me Dorisenone C Miyamoto et al. (1996) reported that the compounds 7α-hydroxyspongian-16-one, 15α, 16α-diacetoxy-11, 12β-epoxyspongian, and 7α-acetoxydendrillol-3 of this species showed cytotoxic activities.

      

    

Epoxygoniolide-1 Fish et al. (2017) reported on the occurrence of compounds such as spongian-16-one, aplytandiene 3, aplysulfurin and aplyroseol 2, and gracilins A, B, C, G, and M from this species. All these metabolites showed cytotoxic activity against Hela S3 cells. Compounds, gracilins B and C, and isomers showed activity against a wide panel of human tumor cell lines.

7α-hydroxyspongian-16-one       15α, 16α-diacetoxy-11, 12β-epoxyspongian

  7α-acetoxydendrillol-3

 

  Aplytandiene 3     Aplysulfurin     Aplyroseol 2

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   Gracilin A       Gracilin B           R=Ac                                     Gracilin C

               R=Ac              R=COPr           Gracilin G           Gracilin M Other compounds: The organic extract of this species yielded five new diterpenes, the activities of which are as yet unknown (White et al., 2016).

1–5: Diterpene 1,  Diterpene 2,  Diterpene 3,  Diterpene 4 (7D, 17D-d​iacet​oxy-1​5,17-​oxido​spong​ian-1​6 -one​),  Di​terpe​ ne 5.

Chromodoris annae (Bergh, 1877)

Order: Nudibranchia Family: Chromodorididae Common name: Anna’s chromodoris

Distribution: Tropical west Pacific and Indian Ocean; from Malaysia, Indonesia, and the Philippines to the Marshall Islands Ecology: This shell-less, benthic species inhabits a depth range of 15–30 m; it is encountered singly on coral reefs during the day. Description: It can reach a maximum size of 5 cm length. Body is elongate with a foot which is distinguished from the upper body by a skirtlike mantle partially hiding the foot. Its rhinophore and branched gills are yellow to orange in color. Background color is varying from bluegray to intense blue with tiny black spots. Its blue dorsal side and the foot are bordered with a black line, which can be discontinuous depending on the specimen. A black dash between the rhinophores distinguishes this species from similar species like Chromodoris elisabethina and Chromodoris westraliensis. Mantle edge and foot are bordered with white and orange to yellow lines. Biology Food and feeding: It is carnivorous, feeding on sponges, polyps, and tunicates. Reproduction: It is a simultaneous hermaphrodite. Both individuals dart their penis towards each other to induce one to act as a male and the other as the female. The first one to successfully penetrate the body wall is the dominant male. Eggs are deposited on a substratum, where they develop and hatch into (planktonic) vestigial veliger larval stage and then develop further as adults. Compound(s) and Activities Cytotoxic/antifungal activity: The compound latrunculin A isolated from this species showed significant cytotoxic activity against three cancer cell lines, viz. murine P388 leukemia, human HT‐29 colon cancer cell line, and human A549 cell line (human Caucasian lung carcinoma) with GI50 values of ∼0.5 μM. Latrunculin B (73) additionally exhibited strong antifungal activity (Ciavatta et al., 2017; Fisch et al., 2017).

               Latrunculin A    Latrunculin B

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Chromodoris aspersa (Gould, 1852) (=Chromodoris inornata)

deoxoscalarin‐3‐one

Order: Nudibranchia Family: Chromodorididae Common name: Purple spotted nudibranch Distribution: Throughout the tropical Indo-West Pacific Ecology: It is a nocturnal species that may be found under rocks during the day. It occurs from the low intertidal to a depth of 37 m in protected to exposed locations. Description: This dorid is elongate with a white body and foot covered with magenta spots, most surrounded by a translucent ring. Rhinophores are yellow-orange, and the gills vary from pale yellow to orange. It attains a maximum length of 4 cm. Biology Food and feeding: It probably feeds on a thin, orange-red sponge. Reproduction: It deposits its eggs with the ribbon attached by its side rather than its edge. Compound(s) and Activities Anticancer activity: The sesquiterpenoids and a mixture of scalaranes isolated from this species have shown anticancer activity against the human KB and the murine L1210 leukemia cell lines, and the GI50 values recorded for the different compounds are given below. Compound

GI50 Values

Inorolide A

∼7 μM

Inorolide B Inorolide C Deoxoscalarin‐3‐one 21‐hydroxydeoxoscalarin 21‐acetoxydeoxoscalarin

∼5 μM ∼4 μM ∼2 μM ∼9 μM ∼1 μM

12‐O‐​acety​l‐16‐​O‐dea​cetyl​‐12,1​6‐epi​scala​rolbu​tenol​ide

∼5 μM

Source:  Fisch et al. (2017).

  Inorolide A     Inorolide B        Inorolide C

       R=OAc; R1=CH2OH     R=OAc; R1=CH2OAc    21-hy​droxy​deoxo​scala​rin    2​1‐ace​toxyd​eoxos​calar​in

12-O-​acety​l-16-​O-dea​cetyl​-12,1​6 -epi​scala​rolbu​tenol​ide

Chromodoris lochi (Rudman, 1982)

Order: Nudibranchia Family: Chromodorididae Common name: Loch’s chromodoris, toothpaste nudibranch Distribution: Tropical Western Pacific; East Africa, Indonesia to Fiji and Tonga Ecology: This benthic, mobile species dwells among algae and coral reefs. Description: C. lochi is blue or blueish-white with a white margin and typically dark or black lines running down the mantle and the foot. On the mantle, a continuous line runs

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around the border, passing on the outside of the rhinophore, and a second median one can be discontinuous. Individuals can reach a size of 4 cm in length. Biology Food and feeding: This heterotrophic species feeds upon specific sponges, barnacles, sea squirts, soft corals, hydrozoans, hydroids, and bryozoans. Association: This species is associated with the sponge species Leiosella levis (=Spongia mycofjiensis) and Hyaella sp. Reproduction: It is a simultaneous hermaphrodite. Both individuals dart their penis towards each other to induce one to act as a male and the other as the female. The first one to successfully penetrate the body wall is the dominant male. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Antihelmintic activity: The compound Latrunculin A isolated from the sponge–nudibranch pair Leiosella levis–Chromodoris lochi showed excellent in-vitro activity at 50 µg/ml against Nippostrongylus brasiliensis, a type of nematode/gastrointestinal roundworm that infects primarily rodents and mainly rats (Kakou et al., 1987; Attaway and Zaborsky, 1993). Cytotoxic activity: This species also had sponge (Hyatella sp.)-derived polyketides, laulimalide (syn. fijianolide B) and isolaulimalide (syn. fijianolide A). These two compounds exhibited cytotoxic stabilizing action and are of interest as antitumor agents (Fisch et al., 2017).

         Laulimalide             Isolaulimalide Anticancer activity: The compound laulimalide of this species showed in-vivo anticancer activity against two xenograft models, human MDA‐MB‐435 breast cancer and the human HT‐1080 fibrosarcoma models (Ciavatta et al., 2017). Others: The sponge–nudibranch pair Spongia mycofijiensis–Chromodoris lochi showed the presence of a novel compound, dendrolasin, the function of which is as yet unknown (Kakou et al., 1987).

Dendrolasin

Chromodoris quadricolor (Ruppell and Leuckart, 1828) (=Glossodoris quadricolor)

Order: Nudibranchia Family: Chromodorididae Common name: Pyjama nudibranch, pyjama slug Distribution: Western Indian Ocean and the Mediterranean Sea: Red Sea to East Africa Ecology: This benthic species is found at depths of 30 m in places close to submarine springs. Description: Body of this species is smooth, dorsoventrally flattened, and brightly colored. Mantle is ovate with a broad overhang of the edge, and the posterior end of the foot extends beyond the mantle when the animal is crawling. Rhinophores are lamellated, and the branchial plume is located mid-dorsally in the posterior part of the notum (dorsal surface of the body). This nudibranch is four-colored, that is, it is yellow, white, blue, and black in color. Notum has two whitish-blue bands and three wider black ones. All around there is a white band, followed by another wider orange band and a white edge. Rhinophores and gills are darker orange than the band on the mantle edge. It attains a size of 5 cm. Biology Food and feeding: It feeds upon specific sponges, barnacles, sea squirts, soft corals, hydrozoans, hydroids, and bryozoans. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum, where they develop and hatch into the (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Anticancer and antifungal activity: The compounds latrunculins A and B have been isolated from this species. The latrunculins bear strong actin-binding properties, thus interfering with the cytoskeleton and inhibiting the proliferation of cancer cells. Latrunculin B additionally exhibited strong antifungal activity (Ciavatta et al., 2017; Fisch et al., 2017).

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Hypselodoris infucata (Rüppell and Leuckart, 1831)

Halgerda stricklandi (Fahey and Gosliner, 1999)

Order: Nudibranchia Family: Chromodorididae Common name: Painted nudibranch Distribution: Indo-Pacific and Mediterranean Sea Ecology: It is found on rocky bottoms of intertidal and shallow subtidal habitats on tropical reefs. Description: Body of this species is elongated, relatively high in the middle, with a narrow overhang of the mantle edges along the sides, and it widens anteriorly. Rhinophores are lamellated and retractile. Gills form a circle of 10–12 plumes posteriorly around the anus. Background body color is cream or greenish. Edge of the notum is pale blue with a line of darker blue and yellow spots. Surface of notum is sprinkled with small yellow dots, dark spots, and an irregular and variable pattern of white pigmentation along the axis. Rhinophores are bright orangered with a white stalk. Gill plumes are white, each with a reddish rachis. It reaches a maximum size of 55 mm.

Order: Nudibranchia Family: Discodorididae Common name: Strickland’s halgerda Distribution: Andaman Sea, Thailand; also in Indonesia, Malaysia, and Myanmar Ecology: It lives in a variety of habitats like mangrove, estuarine, coral reefs, sea-grass beds, lagoons, sand dunes, rocky shores, cliffs, and intertidal mud. Description: This species has large, bright orange–tipped, conical tubercles scattered over the dorsum. There are many smaller orange tubercles scattered amongst the larger tubercles. Rhinophore club is translucent yellow, and there is a black line extending down the whole length of both the rhinophore club and stalk on the posterior midline. Anterior side of the club also has black pigmentation. Gill has black spots on the anterior sides of the four branchial leaves. Foot has an orange margin. Its normal size is 7 cm.

Biology Food and feeding: It is carnivorous feeding on sponges of Dysidea sp. After eating the sponge tissues, the hard bits (spicules) of the sponge are left behind as a skeleton. Reproduction: Painted dory reproduces sexually. It is an oviparous hermaphrodite. The genital opening is on the right side, and the individuals put themselves head to tail for mating. The egg laying is like a ribbon arranged in whitish spirals. The larvae hatch 5 days after hatching and lead a planktonic life that lasts about 3 weeks (Anon., DORIS, http:​//dor​is.ff​ essm.​fr/Es​peces​/ Dori​s-pei​nturl​uree3​).

Biology Food and feeding: It feeds primarily on sponges. Reproduction: Not reported. Compound(s) and Activities Antibacterial activity: The organic extract of this species displayed modest activity against Staphylococcus aureus (Dean and Prinsep, 2017).

Diaulula sandiegensis (Cooper, 1863)

Compound(s) and Activities Cytotoxic activity: The terpenoid furodysinin isolated form this species showed cytotoxicity against HeLa cell line displayed an IC50 at 102.7 µg/mL (Mudianta et al., 2016).

Furodysinin

Order: Nudibranchia Family: Discodorididae Common name: Sea leopard, ringed doris Distribution: Eastern Pacific: from Barkley Sound, British Columbia to Baja, California; Mexico Ecology: It occurs on large rocks in pools, low intertidal zones, and even subtidal zones to a depth of 35 m along rock shores.

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Marine Mollusks

Description: Body texture of this species is hard and described as “gritty.” Ground color of this species varies from white to chocolate brown. Dorsum is marked with brown to almost black rings or occasionally irregular blotches of various sizes, number, and position; most commonly, these rings are arranged in two longitudinal rows, one on either side of median line, with three to four in each row. Rhinophores have 9–30 lamellae. There are six to seven branchial plumes, which are tripinnate and grayish-white to dusky in color, with whitish tips. It attains a maximum size of 150 mm. Biology Food and feeding: It mainly feeds on sponges belonging to the species of Halichondria panacea and Haliclona permollis; and species of Myxilla and Permollis. Reproduction: In this species, the egg ribbon is white, relatively narrow, and attached by one margin under the rock ledges. Completed egg ribbons typically form oval spirals. There are typically one or two eggs per capsule and up to 16 million eggs per ribbon. Compound(s) and Activities Cardiovascular effects: The compound isoguanosine (9-(β-Dribofuranosyl) isoguanine) isolated from this species produces cardiovascular effects in mice and guinea pigs by slowing down the heart and hypotension; and relaxation of smooth muscles in humans (Cimino et al., 1986; Datta et al., 2015).

Common name: Rose nudibranch, black dorid Distribution: Tropical to warm temperate Indo-West Pacific; Zanzibar to Australia, New Caledonia, and Indonesia Ecology: It occurs on lower shores in rocks/sand/reefs; calm areas of bays on rocky coasts, on back reefs and shallow tidal areas of rock and coral rubble. Description: This species is often red, pink, or reddish orange when juvenile, but black when adult. There are five or six large branching gills, which often spread from one side of the mantle to the other, and the small papillae on the skin of the mantle are usually black. It may reach over 10 cm in length. Biology Food and feeding: It feeds on sponges like other members of the genus. Radula is absent. Instead of grasping a chunk of sponge and rasping it to pieces with their radula, these animals first secrete digestive juices on the sponge to partially digest the sponge tissue; then they slurp up the meal with their tubelike buccal mass. Reproduction: It is a simultaneous hermaphrodite. Both individuals dart their penis toward each other to induce one to act as a male and the other as the female. The first one to successfully penetrate the body wall is the dominant male. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage and develop further as adults. Compound(s) and Activities Antibacterial activity: The organic extracts of the egg masses of this species showed antibacterial activity against E. coli, Staphylococcus aureus, and P. aeruginosa (Fisch et al., 2017).

Dendrodoris limbata (Cuvier, 1804)

Isoguanosine

Dendrodoris fumata (Ruppell and Leuckart, 1831)

[email protected] Order: Nudibranchia

David W. Behrens Family: Dendrodorididae

Order: Nudibranchia Family: Dendrodorididae Common name: Limbata Distribution: Endemic to the Mediterranean Sea Ecology: It is mostly hidden under bare stones; sandy habitat; depth range 1–8 m. Description: It is characterized by having a narrow mantle margin and a yellow (or whitish) line around the mantle edge. This species occurs in three color varieties: brown with a yellow notum edge margin, black with a pale notum edge, and a paler variety with many dark patches. Body is oval and

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smooth with a narrow wavy mantle margin. Anterior border of foot is rounded, with a very shallow groove; and posterior border is rounded. Retractile rhinophores bear 25 leaflets in the upper half. There are six tripinnate, retractile gills. Maximum length is 7 cm. Biology Food and feeding: It feeds mainly on sponges of the species Latrunculia magnifica. Reproduction: On the breeding side, it is hermaphroditic. Its egg mass is a delicate whitish rosette which contains several thousand eggs, from which may emerge trochophore larvae or more complex veliger larvae. Compound(s) and Activities Antifungal activity: The compound polygodial isolated form this species has shown antifungal activity against Saccharomyces cerevisiae IFO 0203 and Hansenula anomala IFO 0136 (Fisch et al., 2017).

Polygodial

Armina babai (Tchang, 1934)

purple. Viscera are pinkish in color and sometimes show through the body. This species may emit a potent medicinal odor when handled. Biology Food and feeding: It is carnivorous, feeding on an array of sessile, benthic animals, such as sponges, tunicates, bryozoans, hydroids, anemones, or corals. Reproduction: Like other sea slugs, it is a hermaphrodite, with both male and female reproductive organs. Compound(s) and Activities Antioxidant activity: The butanol extract of this species has shown antioxidant activity. At 10 mg/ml, the values of the total antioxidant activity and DPPH scavenging activity were found to be 51.9% and 75.4%, respectively. As the butanol extract showed concentration-dependent activity and increase in concentration increased the antioxidant activities, butanol extract of this species is a rich source of antioxidants for use as natural antioxidants (Ramya et al., 2014). Antibacterial activity: The organic extracts of this species have shown activity against E.coli (Gram-negative), K. oxytoca (Gram-negative), K. pneumoniae (Gram-negative), P. mirabilis (Gram-negative), Pseudomonas sp. (Gram-negative), P. aeruginosa (Gram-negative), S. paratyphi (Gram-negative), S. typhi (Gram-negative), Staphylococcus aureus (Gram-positive) and V. cholerae (Gram-negative). The maximum zone of inhibition (16 mm dia) was recorded against Pseudomonas sp., and minimum zone of inhibition (4 mm dia) was recorded against P. mirabilis by butanol extracts; acetone extracts showed a moderate activity on the bacterial pathogenic strains with the maximum zone of inhibition (9 mm dia) against V. cholerae and the minimum against E. coli (3 mm dia); hexane extracts showed a good activity with the maximum zone of inhibition (9 mm dia) against S. paratyphi and minimum level (2 mm dia) against S. typhi; and crude ethanol extracts exhibited poor activity and only three strains (E. coli, P. aeruginosa, and S. paratyphi) were inhibited with the minimum zone (Ramya et al., 2014). The MIC (µg/mL) values of different extracts for the different bacterial species are given below.

MIC (µg/mL)

Order: Nudibranchia Family: Arminidae Common name: Big plain armina nudibranch Distribution: Pakistan, India, China, and Japan Ecology: It inhabits intertidal flats, burrowing in soft silty areas near sea grasses. Description: A. babai grows to 50 mm in length and appears flattened, elongated, and narrow posteriorly. It has a yellow sole and smooth mantle. Longitudinal ridges are absent. Body itself appears ashy to whitish gray and is translucent. There are two big spots on the notum that are purplish. Head veil is an ashy color and has papillae that are dark brown. Anterior gills are yellowish white, while the posterior gills appear dark

Acetone Butanol

Ethanol

Hexane

Methanol

200

50

200

>200

25

K. oxytoca K. pneumoniae P. mirabilis Pseudomonas sp. P. aeruginosa S. paratyphi S. typhi S. aureus

200 >200 >200 >200 150 >200 >200 150

100 100 100 25 50 200 150 200

>200 >200 >200 >200 200 200 >200 >200

200 >200 >200 200 >200 >200 >200 100

>200 100 >200 200 100 >200 200 50

V. cholerae

>200

200

>200

200

100

E. coli

Source:  Ramya et al. (2014).

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Marine Mollusks

Actinocyclus papillatus (Bergh, 1878)

Distribution: West coast of North America from Alaska to Santa Barbara, California Ecology: It inhabits low, rocky intertidal and shallow subtidal zones to depths of 25 m. Description: Background color of this shell-less species ranges from translucent white to gray. Mantle is covered in prominent conical papillae which are tipped with milky yellow. There is a milky yellow border to the mantle. Gills and rhinophores are tipped with a color that ranges from orangebrown to a dark maroon. It grows to 35 mm in length.

Order: Nudibranchia Family: Actinocyclidae Common name: Not designated Distribution: Tropical Western Indo-Pacific Ocean Ecology: It inhabits coral rubble and is seen intermediately between the land and the sea; not entirely terrestrial and not entirely marine. Description: It has a tough leathery mantle, with a circlet of many short gills held in a cup-shaped arrangement. Body is covered with many large rounded tubercles. It varies in color depending on the shade of the brown background color and the density of the cream white speckling scattered all over. Some animals are brown with little creamy speckling, while others are mainly cream white with only patches of the brown background color showing through. This species grows to at least 10 cm in length.

Biology It feeds on compound ascidians and on bryozoans such as Alcyonidium spp. It lays its eggs in whorled ribbons of capsules which stand on edge on the rocks they are laid on. The eggs are white to cream in color. Compound(s) and Activities Antibiotic activity: Acanthodoral (derived from nanaimoal and/or isoacanthodoral) sesquiterpene aldehydes derived from this species exhibited strong antibiotic activity (Zhang and Koreeda, 2004; Tringali, 2003).

Biology This well-camouflaged nudibranch feeds on sponges. Compound(s) and Activities Cytotoxicity: An isonitrile lipid, actisonitrile, obtained from the mantle of this species exhibited moderate cytotoxicity to a mammalian cell line (Dean and Prinsep, 2017).

       1       2         3 1: Acanthodoral;  2: Nanaimoal;  3: Isoacanthodoral

Adalaria loveni (Alder and Hancock, 1862)

Actisonitrile

Acanthodoris nanaimoensis (O’Donoghue, 1921)

Order: Nudibranchia Family: Onchidorididae Common name: Wine-plumed spiny doris, wine-plumed dorid, Nanaimo-horned dorid, red-gilled dorid, Rufoustipped nudibranch

Order: Nudibranchia Family: Onchidorididae Common name: No common names found Distribution: This species is confined to Norway and Sweden; Northeast Atlantic: Europe Ecology: It inhabits kelp forests in shallow water. Description: Body of this species may be white or yellow in color. Mantle is covered by rounded or large flattened tubercles, which are very variable in size. Rhinophores are lamellate. It grows up to 32 mm in length. Biology It appears to feed on Membranipora membranacea on kelp fronds. It is a simultaneous hermaphrodite. Both male and

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female individuals dart their penis towards each other to induce one to act as a male and the other as the female. The first one to successfully penetrate the body wall is the dominant male. Eggs are deposited on a substratum where they develop and hatch into (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Cytotoxicity: Lovenone, a degraded triterpenoid isolated from this species, displayed modest in-vitro cytotoxicity against human ovarian carcinoma (HEY) (ED50, 11 µg/mL) and human glioblastoma/astrocytoma (U373) (ED50, 11 µg/mL) cell lines (Tringali, 2003).

Compound(s) and Activities Antitumoral activity: The compounds 9-chloro-phorbazole D and N1-methyl-phorbazole A isolated from this species exhibited cytostatic effects against several human tumor cell lines (HTCLs) (Dean and Prinsep, 2017).

    9-chloro-phorbazole D    N1-methyl-phorbazole A

Hexobranchus sanguineus (Ruppell and Leuckart, 1828)

Lovenone

Aldisa andersoni (Gosliner and Behrens, 2004)

Order: Nudibranchia Family: Cadlinidae Common name: Not designated Distribution Sri Lanka and India Ecology: It inhabits sublittoral regions. Description: Body of this species is oval, and the notal surface is covered with a series of low conical tubercles. Tubercles form distinct ridges running longitudinally along the center of the notum and perpendicular laterally along the margin of the notum. Rows of these tubercles are situated in regions of opaque blue pigment. These regions are separated by areas of black. There is an opaque, bright-yellow saddle across the notum behind the rhinophores. This saddle extends right to the edge of the mantle. A few bright-yellow patches may partially encircle the gill pocket. Some specimens have yellow patches posterior to the rhinophores. These animals have a size range of 20–30 mm. Biology It feeds mainly on sponges of the family Hyme­desmiidae.

Order: Nudibranchia Family: Hexabranchidae Common name: Spanish dancer Distribution: Tropical and subtropical waters of the IndoPacific; from eastern coasts of Africa, Red Sea, to Hawaii; from south Japan to Australia Ecology: It lives in rocky and coral reefs with many sponges and shelters at depths of 1–50 m. Description: It is a large dorid nudibranch which can grow up to a maximum length of 60 cm. Its body coloration is generally orange-red speckled with multiple small white dots, but it also can be uniformly bright red or yellow with red scattered spots. Body is soft and flattened, anterior dorsal portion has a pair of retractable rhinophores, and posterior part has six contractile gills inserted independently in the body. There is a pair of oral tentacles provided with large digital lobes. Its gills do not have a gill pouch into which the gills can retract. Also, each gill is inserted separately into the body wall. Biology Behavior: It displays a spectacular swimming response. It throws its body into sweeping dorsoventral flexions, creating synchronous undulations through its broad and vividly patterned red-and-white mantle. Food and feeding: It feeds mainly on sponges of Halichondria sp., which provides a potent chemical defense for this species. Reproduction: It is hermaphrodite and is sexually active throughout the whole year. Sex occurs when two nudibranchs

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align themselves up side by side, called copulation, where the male then exchanges sperm sacs. After sex, it may take moments or days before it is ready to lay eggs. Eggs are deposited as coiled rosettes on rocks and coral rubble. Eggs hatch and larval stages appear. Since their life expectancy is only 1 year, they will mature very fast (Anon., http:​//bio​web.u​wlax.​ edu/b​io203​/f201​3/yur​k _dev​i/rep​roduc​tion.​htm).​ Compound(s) and Activities Antitumor activity: The compound sanguinamide B of this species has shown antitumor activity (Blunt et al., 2016; Marsault and Peterson, 2017).

R1=O; R2=OH (Ulapualide C) R1=OH; R2=O (Ulapualide D)

Ulapualide E Sanguinamide B Cytotoxic activity: The compound ulapualide A (a macrolide) exhibited cytotoxic activity against L1210 murine leukemia cells (Pati et al., 2015).

Ulapualide A The compounds ulapualides (A–E) have been isolated from the egg masses of this species. Among them, Ulapualide C demonstrated submicromolar cytotoxicity against select NCI cell lines (768-0, DU-145, MDA-MB-231, and A549), with the most potent activity against MDA-MB-231 cells (IC50 0.58 μM). Ulapualides A and B were found to be two to four-fold more potent than ulapualide C (Parrish et al., 2017).

Ulapualide B

Anticancer activity: Ciavatta et al. (2017) reported that the compounds Ulapualides A and B of this species displayed anticancer activity against murine L1210 leukemia cells with GI50 values of ∼10 and ∼30 nM, respectively. Compounds possessing anticancer activity such as kabiramides A–E, halichondramide, dihydrohalichondramide, tetrahydrohalichondramide, and 33‐methylhalichondramide have been isolated from this species. Kabiramides A and B were active with GI50 values of ∼10 nM, and kabiramides D and E with GI50values of ∼30 nM in the same cancer cell line. Kabiramide C displayed in-vitro growth inhibitory effects that are ten-fold higher in human MCF‐7 breast cancer cells (GI50 = ∼0.5 μM) than in human fibroblasts (GI50 = ∼8 μM). This compound appears to display a certain level of bioselectivity. The bioselectivity of kabiramide G is even more pronounced, with GI50 values of 0.02 μM in MCF‐7 cancer cells and >2 μM in human fibroblasts (Ciavatta et al., 2017).

Halichondramide displayed the GI50 value of 10 µM for compound 3 (White et al., 2015).

and separated in large animals. Intensity of its pink coloration (and green-gray tones) is related to diet and time since feeding. Other distinguishing characters of this species are the pale pink edge to the mantle; broad, triangular, black-tipped oral tentacles; and rhinophoral clavus with 22–26 lamellae (particularly in animals greater than 35 mm). It attains a maximum length of 6.0 cm. Biology Food and feeding: Like all phyllidiids, it is a sponge feeder on sponges of the genera Acanthella, Halichondria, Axinella, and Axinyssa. It also grazes on coral encrusted by algae. Reproduction: It is a simultaneous hermaphrodite. Eggs are laid in a flattened ribbon and are deposited on a substratum where they develop and hatch into a (planktonic) vestigial veliger larval stage before developing further as adults. Compound(s) and Activities Compounds: The sponge (Acanthella cavernosa)-derived metabolites axisonitrile 3 and axisothiocyanate 3; 10-isothiocyano-4-cadinene and 10-thiocyanato-4-cadinene; diterpenes amphilectene, kalihinol A and kalihinol E; 3-isocyanotheonellin, 9-isocyanopupukeanane; and a new molecule with an isocyano group have been isolated from this species (Fisch et al., 2017; Wright, 2003).

         

    

 

         Axiso​ nitri​ le-3 ​      Axiso​ thioc​ yanat​ e-3         1         2         3        4

Phyllidiella pustulosa (Cuvier, 1804)

        

            

           R​ =NCS                ​ R=SCN​  10-isothiocyano-4-cadinene  10-isothiocyano-4-cadinene 

Order: Nudibranchia Family: Phyllidiidae Common name: Pimpled phyllidiella, vesicular sea slug, pustulose wart slug Distribution: Throughout the tropical Indo-West Pacific Ecology: This benthic species inhabits coral reefs of intertidal and subtidal areas; depth range 6–38 m. Description: P. pustulosa changes in appearance as it grows. Tubercles are in a cluster, which is amalgamated in juveniles

    

 

         Amphi​ lecte​ ne       Ka​ lihin​ ol-A

             ​Kalih​inol-​E     3-i​socya​nothe​onell​in

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R1=NC, R2=H      Molecule with an isocyano group 

Caryophyllene 9-isocyanopupukeanane Antiplasmodial activity: Among the said compounds, 10-isothiocyano-4-cadinene showed moderate antiplasmodial activity (IC50 1.5 μg/ml towards Plasmodium falciparum clones K1, and NF54) (Fisch et al., 2017; Wright, 2003). Cytotoxic activity: Among the compounds, axiisonitrile3R=CN, an axinisothiocyanate K derivative, and a new molecule with an isocyano group of this species were found to be moderately cytotoxic (Fisch et al., 2017).

Compound(s) and Activities Anticancer activity: The carbonimidic chlorinated sesquiterpenes reticulidins A and B isolated from this species displayed anticancer activity against the cancer lines. The in-vitro GI50 values displayed by these compounds were ∼1 μM in KB cells, and ∼2 and ∼0.3 μM in mouse L1210 leukemia cells, respectively (Ciavatta et al., 2017; Tanaka and Higa, 1999).

           Reticulidin A       Reticulidin B

2.3 CLASS: CEPHALOPODA Sepioteuthis lessoniana (Férussac, 1831)

Reticulidia fungia (Brunckhorst and Gosliner in Brunckhorst, 1993)

Order: Nudibranchia Family: Phyllidiidae Common name: Warty nudibranchia Distribution: Indo-West Pacific: Fiji, Micronesia, Eastern Australia, Taiwan, Christmas Island, Bali Ningaloo Reef, Western Australia Ecology: It is found in back reef, flat reef, reef slopes, and lagoons; depth range 1–20 m. Description: It has broad-based ridges which are few in number. The base of these ridges has a fine, white border. Mantle margin is broad and blue-gray in color. It has a single black line around the side of its foot, occurring slightly above its gills. Rhinophores have 14–18 lamellae. This species grows to a maximum length of 40 mm. Biology Food and feeding: It is carnivorous, feeding mostly on sponges, ascidians, and stinging hydroids. Reproduction: It is a simultaneous hermaphrodite. Eggs are deposited on a substratum where they develop and hatch into a (planktonic) vestigial veliger larval stage before developing further as adults.

Phylum: Mollusca Class: Cephalopoda Order: Myopsida   Family: Loliginidae Common name: Bigfin reef squid, oval squid, inshore squid Distribution: Indo-Pacific: From Japan to Australia and New Zealand coasts; from Hawaii to the East African coast; north to Red Sea and south to Madagascar; introduced in the Mediterranean Sea Ecology: It is a demersal neritic species inhabiting warm, shallow coastal waters, rock reefs, seaweeds, and estuaries. It is primarily active at night and moves to deeper waters or in proximity to floating driftwood, reefs, rocks, or sea grasses during daylight; often solitary; depth range 0–100 m. Description: Body of this species is fusiform in shape, with a large mantle, attached head, and multiple arms. Its main body mass is contained in the mantle (sometimes referred to as the “hood”). Mantle is a highly muscular organ which surrounds the entire body of the squid. Fins are located on the superior portion of the mantle; they extend along over 90% of the length of the mantle and give the squid a characteristic oval appearance. Eight arms (not generally of identical length) and two tentacles are attached to the bottom portion of the head. Each of the arms is lined with toothed suction cups, and the two tentacles possess toothed suction cups at their distal end. Maximum reported mantle length in males is 422 mm and 382 mm in females. Maximum weight is 2 kg. Biology Food and feeding: It is a voracious and strictly carnivorous species. It mainly consumes mollusks, fish, and prawns. It utilizes its characteristic tentacles to catch live prey. It exhibits cannibalism on smaller conspecifics or among size classes.

Marine Mollusks

Reproduction: It is a gonochoric species. Male and female adults usually die shortly after spawning and brooding, respectively. Males perform various displays to attract potential females for copulation. During copulation, the male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. After laying, females coat the eggs in a gelatinous substance, forming an egg capsule. Egg capsules incubate for about 3 weeks, depending on temperature. The incubation period can last anywhere between 15 and 22 days. Upon hatching, the paralarvae are planktonic and are about 4.5–6.5 mm in mantle length (excluding tentacles), with fully functioning fins and ink sacs. They resemble miniature adults and are already strong swimmers. Compound(s) and Activities Hepatoprotective activity: The β-Chitosan isolated from this species, which possesses antioxidant and antilipidemic properties, showed hepatoprotective activity against carbon tetrachloride (CCl4)-induced oxidative stress in Wistar rats (Nair et al., 2015). Antibacterial activity: The extracts of accessory nidamental gland of this species showed different levels of antibacterial activity against E. coli, A. hydrophila and Staphylococcus aureus. Among the four extracts, butanol extract showed the maximum antibacterial activity, followed by methanol extract. Maximum antibacterial activity was found in ripe stage, especially in butanol extract against E. coli (10.1 mm), and minimum activity was found in ethanol extract against A. hydrophila (3.0 mm) in the maturing stage (Venkatesan et al., 2014). The chitosan derived from this species showed maximum inhibition of 14 mm against S. aureus and minimum inhibition of 8 mm against K. pnemoniae and V. cholerae. The sulphated chitosan (SCL) showed maximum inhibition of 14 mm against V. cholerae and E. coli. The phosphorylated chitosan (PCL) showed maximum inhibition of 13 mm against V. cholerae and S. pnemoniae. These findings suggest that the chitosan and the derivatives of this species could be used as an alternative antibacterial agent (Subhapradha et al., 2013a).

Doryteuthis (Amerigo) pealeii (Lesueur, 1821) (=Loligo pealii)

Class: Cephalopoda  Order: Myopsida  Family: Loliginidae Common name: Longfin inshore squid Distribution: North Atlantic; from Newfoundland to Gulf of Venezuela

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Ecology: It occurs over the continental shelf and upper slope from the surface down to about 400 m in depth, but is rare or absent around islands; schools in continental shelf and slope waters; lays eggs in shallow waters near shore. Description: These medium-sized squid grow to about 50 cm long. Like all squid, they have ten arms (eight of which are the same length, while one pair used for grabbing prey are longer). Mantle of this species is long, moderately slender, and cylindrical, and the posterior end is bluntly pointed. Fins are rhomboidal and their sides nearly straight. This species of squid is often seen with a reddish hue but, like other species of squid, it can manipulate its color so it can vary in color from a deep red to a soft pink. Maximum mantle length is 50 cm in males and approximately 40 cm in females. Biology Behavior: It has the ability to change its color and color patterns instantly. It is thought that as well as using this color/ pattern transformation as a defense mechanism, it is also a communication technique that may be employed in courtship. Further, their speed and maneuverability have earned them the description of “invertebrate athletes.” Food and feeding: L. pealeii is carnivorous. Its diet includes chaetognaths, crustaceans, decapod shrimp, fish, polychaetes, other squid, and euphausids. Cannibalism is common in this species. Predators: The species is preyed upon by yellowfin tuna (Thunnus albacares), toothed whales, and other pelagic predators. Reproduction: This species exhibits sexual dimorphism, with most males growing faster and reaching larger sizes than females. Maturity is attained at about 15 cm in males and 13 or 14 cm in females. Mature squid are encountered almost throughout the year, but two peak spawning periods are generally observed: the first and more important in spring, and the second, less intense, in late summer and fall. Eggs are laid in gelatinous, fingerlike strands, many of which are attached together in large masses to solid substrates (i.e. rocks, shells, shipwrecks) in depths of 10–250 m. The eggs hatch into planktonic larvae and juveniles, and there is no metamorphosis. Compound(s) and Activities Antitumor activity: The organic extracts of this species have shown antitumor activity in vivo (Anon., http:​//sho​dhgan​ ga.in​fl ibn​et.ac​.in/b​itstr​e am/1​0 603/​38427​/ 7/07​_ chap​t er%2​ 02.pd​f ). Antimicrobial activity: The microbial community of the accessory nidamental gland and egg case of this species has shown antimicrobial activity. The butanol-ANG (accessory nidamental gland) extracts of this species has inhibited the growth of various bacterial pathogens including V. anguillarum and Streptomyces griseus (Barbieri et al., 1997).

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Uroteuthis duvaucelii (d’Orbigny [in Férussac & d’Orbigny], 1835) (=Loligo duvauceli)

Order: Myopsida

Family: Loliginidae

Common name: Indian Ocean squid, Indian squid Distribution: Indo-West Pacific; throughout the Indian Ocean to Malaysia and the South China Sea; Red Sea and Arabian Sea Ecology: It is a neritic (shallow water), demersal, and reef associated species; depth range 3–170 m.

can be observed on hectocotylized arm in male. Sex ratio of male to female is 1:2. The fertilized female has average fecundity about 2,000 to 10,000 eggs. After fertilization, female will deposit numerous egg capsules on suitable substrates in 5–7 days. The maximum length of this species is about 400 mm (Petsut and Kulabtong, 2013). Compound(s) and Activities Anticancer activity: The methanol extracts of the internal bone of this species displayed anticancer activity against HepG2 liver cancer cells. Minimum toxicity of 32% was observed at 100 µg and maximum of 42% was observed at 1000 µg concentration and IC 50 at a concentration of >1000 µg. The percentage of toxicity showed an increasing trend with increasing concentration of the extract (Diaz et al., http:​ //ijp​sr.co​m /bft​-arti​cle/i ​n-vit ​r o-cy ​totox ​ic-ac​t ivit ​y-of-​s quid​ -and- ​cuttl​efish​- bone ​- extr​a ct-o​n -hep ​-g2-c​ell-l ​i ne/?​v iew=​ fullt​ext).​ Anticoagulant activity: The organic extracts of this species showed anticoagulant activity with 376.98 USP units/mg (Periyasamy et al., 2013).

Loligo vulgaris (Lamarck, 1798)

Description: Mantle of this species is long, slender, and tubular and tapers from a middle and blunt posterior end. Fins, which are rhomboidal, are restricted to the posterior end of the mantle. Its narrow head possesses ten arms, including the two long slender tentacles. Distal half of the left arm of the male is hectocotylized, and gladius is narrow and slightly brownish in color. Ink sac possesses two small light organs one on either side. Coloration of body is reddish with brown chromatophores. Its maximum length is 29.0 cm, maximum published weight is 1.5 kg, and maximum reported age is 3 years. Biology Food and feeding: This species is considered to be a carnivorous and selective feeder. It prefers the zoea stage of the blue swimming crab Portunus pelagicus, and post larva of penaeid shrimps such as Penaeus vannamei. Reproduction: During brooding, fertilized embryos hatch into a planktonic stage, migrating into the upper layers of the water column. As they grow larger, they take up a benthic existence as adults. Spawning occurs throughout the year but mainly in spring and autumn. During copulation, a male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. Adult males usually then die shortly after spawning, whilst females survive for a short while until after brooding. The life cycle of U. duvaucelii lasts around 1 year, although this can vary due to environmental factors. In Thailand, this species is able to spawn annually. The average size of mantle length (ML) of spawners ranges from 4.3 to 10.0 cm, and external sex characteristics of the squid

Order: Myopsida

Family: Loliginidae

Common name: European squid or common squid Distribution: From the North Sea to at least the west coast of Africa Ecology: It is a neritic, semidemersal species, which undertakes distinct horizontal and vertical migrations, depending on the environment; lives from sea level to depths of 500 m. Description: It has a long, moderately slender and cylindrical body. Rhomboid fins comprise two-thirds of the mantle length, though locomotion is via jet propulsion. Posterior border is slightly concave. Head is relatively small and has large eyes which are covered with a transparent membrane. Among its ten limbs, which surround the mouth and beak, eight are relatively short arms, and two form the tentacles. Fourth left arm of males is a hectocotylus. This species can grow up to 40 cm in mantle length. Color of the European squid is grayish-transparent or reddish, depending on the expansion of

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chromatophores in the dermis. Males have small chromatophores on their mantle. Biology Food and feeding: The two tentacles are long and are used to catch prey. They feed late during the night and/or during the early morning. They have been reported to prey upon different organisms according to their size. Squid of 69–125 mm dorsal mantle length feed mainly on euphausiids (95%), and those of 126–240 mm mainly on fish, with Bregmaceros sp. and hake as important components (Lipiński, 1987). Reproduction: It is a gonochoric species. Males are generally bigger than the females and exhibit more rapid rates of growth. Male and female adults usually die shortly after spawning and brooding, respectively. Males perform various displays to attract potential females for copulation. During copulation, the male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. Embryos hatch into the planktonic stage and live for some time before they grow larger and take up a benthic existence as adults. The spawning peaks in the Central Adriatic Sea were between January and May, but mature individuals were caught in all months, indicating that in this area, this species spawns throughout the year (Šifner and Vrgoč, 2004). Compound(s) and Activities Hemolytic activity: The ink extract of this species exhibited a maximum hemolytic activity of 128 hemolytic units against tested erythrocytes (Nadarajah et al., 2017). Antioxidant activity: In DPPH assay, the ethanolic extract of the ink of this species has exhibited an antioxidant activity of 83.5% (Nadarajah et al., 2017). Antibacterial activity: The ink of this species was found to be a potent antibacterial agent against the pathogens tested. 200 μL of ink extract showed remarkable antibacterial activity as zone of inhibition against E. coli (28 mm), K. pneumoniae (22 mm), P. aeruginosa (21 mm), and Staphylococcus aureus (24 mm) (Nadarajah et al., 2017). Anti-inflammatory properties: The 68.9% inhibition of protein denaturation by its ink extract indicated that it has very good in-vitro anti-inflammatory properties (Nadarajah et al., 2017). The ethanolic extracts of the ink of this species indicated the presence of functional groups such as 1° and 2° amines, amides, alkynes (terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic acids, and alkyl halides, which complements the biochemical background of therapeutic applications.

Loligo sp. Traditional uses: Ahmad et al. (2018) reported that the shell of this species has shown medicinal uses. Tea made from boiling the shell powder has been reported to cure asthma.

Dosidicus gigas (Orbigny, 1835)

Order: Oegopsida Family: Ommastrephidae Common name: Humboldt squid, jumbo squid, jumbo flying squid Distribution: Eastern Pacific Ocean; Oregon, Washington, British Columbia, and Alaska Ecology: It is found at depths of 200–700 m. Description: It is one of the largest squid, reaching a mantle length of 2.5 m, and weighs up to 50 kg. Mantle is very large, robust, and thick-walled. Fins are rhomboidal, muscular, and broad. Distal end of arms (adults especially) is drawn out into very long, attenuate tips with 100–200 minute, closely packed suckers. Biology Food and feeding: The diet of jumbo squid includes fish, crustaceans, and mollusks (pteropods and cephalopods). Reproduction: D. gigas only has one reproductive cycle during its lifetime, so it is known as monocyclic. Spawning occurs throughout the year, with peaks from October through January in the southern hemisphere. Fertilization takes place inside the female. Females produce floating egg masses. Each gravid female can produce 3–20 such masses (Nigmatullin et al., 2001). Compound(s) and Activities Antihypertensive, anticancer, and antioxidant activities: The bioactive hydrolysates (produced using commercial proteases such as protamex, trypsin, neutrase, savinase, NS37005, esperase, and alcalase) of the gelatin of this species showed antihypertensive, anticancer, and antioxidant activities. The Alcalase hydrolysate was the most potent angiotensin-converting enzyme (ACE) inhibitor (IC50 = 0.34 mg/mL), while the esperase hydrolysate showed the highest cytotoxic effect on cancer cells, with IC50 values of 0.13 and 0.10 mg/mL for MCF-7 (human breast carcinoma) and U87 (glioma) cell lines, respectively. Further, the radical scavenging capacity of gelatin increased approximately three-fold for protamex, neutrase, and NS37005 hydrolysates and between seven and ten-fold for trypsin, savinase, esperase, and alcalase hydrolysates. Trypsin, savinase, esperase, and alcalase hydrolysates had a metal chelating capacity above 80%, whereas protamex, neutrase, and NS37005 hydrolysates registered less than 25%. The antioxidant activity measured by FRAP (ferric ion reducing power) was largely unaffected by the enzyme used, increasing approximately two-fold for all hydrolysates. The

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most active hydrolysates (alcalase and esperase) were comprised mostly of peptides with molecular weights ranging from 500 to 1400 Da (Alemán et al., 2011a). Antioxidant and ACE-inhibitory activities: The synthetically derived peptides of the inner and outer tunics of this species have been reported to enhance the scavenging activities of peptides. Further, the synthetic peptides (I and III) showed ACE inhibitory activity. Among these peptides, peptide I showed the most potent effect (IC50 90.0 μM), followed by peptide III (IC50 256.8 μM) (Alemán et al., 2011b).

Biology and Ecology of Pharmaceutical Marine Mollusks

16316​3/0).​Embryos hatch into the planktonic stage and live for some time before they grow larger and take up a benthic existence as adults. Compound(s) and Activities Anti-inflammatory activity: The melanoprotein of this species has shown anti-inflammatory activity, evidenced by reduced paw edema in the treatment of 10 and 20 mg/kg in the paw edema assay (Ahmad et al., 2018).

Sepia aculeata (Van Hasselt, 1835) Ommastrephes bartramii (Lesueur, 1821)

Order: Oegopsida Family: Ommastrephidae Common name: Neon flying squid, red flying squid, akaika, red squid Distribution: Subtropical and temperate oceanic waters globally; Pacific, Atlantic, and Indian Oceans Ecology: It is a benthopelagic species; depth range 0–1,500 m. Description: It is easily distinguishable by the presence of an elongated silver-colored band in the middle of the ventral side of the mantle. Adult males usually have a mantle length of 29–32 cm but can reach the maximum length of 45 cm. Adult females are much larger, usually having a mantle length of around 50 cm with the maximum known length being 60 cm. Hectocotylus develops from the left or right fourth arm. There are four to seven toothed suckers on the tentacular club, near the nearest carpal suckers. Photophores are present but are small, irregular, and restricted to the ventral side of the mantle, head, and tentacles. It lives up to only 1 year.

Order: Sepiida Family: Sepiidae Common name: Needle cuttlefish Distribution: Indo-West Pacific: Southern India to Japan and the Philippines Ecology: This benthic species occurs from shore to a depth of 60 m. Biology: Mantle of this species is about half as broad as long, and tentacular club is long and slender with 10–12 minute, subequal suckers in each row across the club in males, 13–14 suckers across in females. Left arm IV is hectocotylized, and there are about 12 normal suckers (three series) proximally followed by about five or six series of very small suckers in ventral longitudinal rows. Dorsal mantle has a fine, dark-pigmented, transverse, reticulate color pattern, and a pale reflective line is seen along bases of fins. It has a maximum length of 23 cm and weight of 1.3 kg.

Biology Food and feeding: This species is an active predator, feeding principally on myctophids, sternotychids, sauries, and, to a lesser degree, on juveniles of predatory fish, flying fish, pelagic shrimps, amphipods, and euphausiids and conspecific juveniles. Reproduction: It is gonochoric. Spawning in the North Pacific occurs throughout the year, with peaks in autumn and winter–spring. Oocytes in females probably develop asynchronously, with spawning occurring intermittently over a prolonged period of time, and egg masses are unknown. The potential batch fecundity of females is at least 1.4 million small eggs (Anon., http:​//www​.iucn​redli​st.or​g/det​ails/​

Biology Food and feeding: Prawns and other crustaceans such as crabs are the dominant food of this species. It also feeds on fish, polychaetes, and other cephalopods. Reproduction: The sex ratio of males to females is almost equal. Individuals with gonads in maturing and mature stages are met with in all seasons of the year. Males attain maturity at the age of 7–9 months and females at 10–12 months along the east coast of India. Spawning takes place in females throughout the year (at Mandapam, India), with peak activity from August to March. During the spawning season, clusters of egg capsules are attached to gorgonids (Silas et al., 1984).

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Compound(s) and Activities Antimicrobial activity: A potential polysaccharide extracted from the cuttlebone of this species showed antimicrobial activity against B. subtilis, E. coli, K. pneumoniae, V. cholerae, V. parahaemolyticus, Staphylococcus aureus, P. aeruginosa, S. typhii and Shigella sp.; and fungal species Candida sp., Rhizopus sp., Aspergillus flavus, and Aspergillus fumigatus at different concentrations such as 25%, 50%, 75%, and 100%. The activities were found to increase with the increasing concentration of the extracts. The ink samples of this species also showed antifungal activity (Datta et al., 2015). Antioxidant activity: The polysaccharide extracted from the cuttlebone of this species showed antioxidant activity. The values of DPPH, superoxide, and hydroxyl radical scavenging effect of polysaccharides were found to be 36.27% at 10 mg/ ml, 59.57% at 0.5 mg/ml, and 45.86% at 3.2 mg/ml, respectively. The chelating effect of polysaccharides was 48.61% at 10 mg/ml (Subhapradha et al., 2014). Anticoagulant activity: The crude extracts of this species showed anticoagulant activity with 376.98 USP units/mg (Periyasamy et al., 2013).

Sepia brevimana (Steenstrup, 1875)

Order: Sepiida Family: Sepiidae Common name: Shortclub cuttlefish Distribution: Indo-West Pacific: Southern India to Andaman Sea, Gulf of Tonkin, Java, Sulu, and Celebes seas Ecology: It is a demersal species that inhabits coastal and shelf waters; depth range 10–100 m. Description: In this species, mantle lengths range between 40 and 95 mm. Cuttlebone inner cone forms a raised ledge posteriorly. Biology Food and feeding: It eats small mollusks, crabs, shrimp, fish, octopus, worms, and other cuttlefish. Reproduction: The sex ratio of this species is typically 1:2 (M:F). Off India, both sexes attain similar maximum ML at 50% maturity; for example, off southeast India, it was 56 mm (males) and 59 mm (females), and off northeast India, it was 59 mm (males) and 63 mm (females). In eastern India, spawning takes place all year, with spawning peaks between July

and February. Hatchlings reach adult size in approximately 1 year (Anon., http:​//www​.iucn​redli​st.or​g/det​ails/​16259​4/0).​ Male and female adults usually die shortly after spawning and brooding, respectively. Males perform various displays to attract potential females for copulation. During copulation, the male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. Embryos hatch into the planktonic stage and live for some time before they grow larger and take up a benthic existence as adults. Compound(s) and Activities Antimicrobial activity: The polysaccharide isolated from this species showed antimicrobial activity against B. subtilis, E. coli, K. pneumoniae, V. parahaemolyticus, Staphylococcus aureus, P. aeruginosa, S. typhii, and Shigella sp.; and Candida sp., Rhizopus sp., Aspergillus flavus, and Aspergillus fumigatus at different concentrations such as 25%, 50%, 75%, and 100%. The activities were found to increase with the increasing concentration of the extracts. The highest and lowest activity was recorded against P. aeruginosa and E. coli, respectively. In the antifungal activity study, maximum activity and minimum activity were observed against A. flavus and A. fumigatus, respectively. (Datta et al., 2015). Mohanraju et al. (2013) reported that the methanolic extracts from the body tissues of this species showed antibacterial activity against five human pathogens: Grampositive Staphylococcus aureus MTCC 96, B. subtilis MTCC 441; and Gram-negative E. coli MTCC 443, V. cholerae MTCC 3906, and K. pneumoniae MTCC 109. At 100 µl concentration, K. pneumoniae recorded an inhibition zone of 19 mm. Anticoagulant activity: The crude extracts of this species showed anticoagulant activity with 421.72 USP units/mg (Periyasamy et al., 2013).

Sepia esculenta (Hoyle, 1885)

Order: Sepiida Family: Sepiidae Common name: Golden cuttlefish Distribution: Western Pacific: South and East China seas, Japan to Philippines and Indonesia

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Ecology: This species is demersal and inhabits sandy substrates; it is a oceanodromous species; sometimes found burrowing in the substrate; depth range 10–150 m. Description: Mantle of this species is broadly oval; dorsal anterior margin is triangular, obtuse; and ventral mantle margin is emarginate. Arm suckers are tetraserial. Hectocotylus is present on left ventral arm. There are 56 rows of normalsize suckers proximally and 6 rows of reduced suckers medially. Cuttlebone outline is elliptical; bone bluntly rounded anteriorly and posteriorly; dorsal surface is convex posteriorly, flat anteriorly; and spine is present. Coloration of body is light brown with whitish mottle. Dorsal mantle has faint lightcolored wavy transverse stripes and dark spots or blotches. Fins have a pale golden iridescent line along base, both dorsally and ventrally. It attains a maximum length of 18 cm and weight of 600 g.

Sepia kobiensis (Hoyle, 1885)

Biology Food and feeding: It feeds on crustaceans and small fish. Reproduction: Individuals often move into deep water during winter and return to shallow waters in spring to spawn. Spawning has been reported to occur between spring and early summer. Males guard females and, prior to mating, the male gives colorful displays. The eggs are often laid onto elongate substrates such as seaweeds. The sticky egg cases accumulate debris as camouflage. Depending on water temperature, the direct developing young hatch in about 30–80 days (Anon., http:​//www​.iucn​redli​st.or​g/det​ails/​16266​6/0).​

Order: Sepiida Family: Sepiidae Common name: Kobi cuttlefish Distribution: Indo-West Pacific: from Japan to Persian Gulf Ecology: This benthic, oceanodromous species occurs at subtidal depths of 71–200 m; it occurs at the low tide mark. Description: All arms of this species are of similar length, and suckers on all arms are tetraserial. It has 6–12 series of normal suckers proximally and 7–10 series medially, which are reduced, with those on the distal remainder of the arm normal in size. Club suckers differ only slightly in size. It attains a maximum length of 9 cm.

Compound(s) and Activities Antiproliferative activity: The polysaccharide isolated from the ink sample of this species not only suppressed proliferation and migration of MDA-MB-231 cells and expression of MMP-2 and MMP-9 proteins, but also promoted inhibition of cisplatin on proliferation, migration, and MMPs expression of MDA-MB-231 cells, which indicates synergy inhibition of drug combination of this ink polysaccharide and cisplatin on breast cancer cells. The median-effect concentrations of cisplatin and ink polysaccharide were 4.9 and 1659.6 μg/ml, respectively. These findings demonstrated that ink polysaccharide repressed proliferation and metastasis of MDA-MB-231 cells and promoted the anticancer effect of cisplatin on the breast cancer cells. The data suggested that the ink polysaccharide of this species is a potential natural drug that can be used as an auxiliary medicine alongside chemotherapy in treating breast cancer (Liu et al., 2016). Anticarcinogenic properties: The ink oligopeptide of this species significantly inhibited the proliferation of DU-145, PC-3, and LNCaP cells in a time- and dose-dependent manner. Exposing of DU-145, PC-3, and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3), and 5.05% to 16.11% (LNCaP), respectively (Huang et al., 2012).

Biology Food and feeding: It feeds on crustaceans and small fish. Reproduction: It is gonochoric. Male and female adults usually die shortly after spawning and brooding, respectively. Males perform various displays to attract potential females for copulation. During copulation, the male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. Embryos hatch into the planktonic stage and live for some time before they grow larger and take up a benthic existence as adults. Compound(s) and Activities Wound-healing property: The acid-soluble collagen (ASC) developed from this species showed wound-healing property in Wistar rats. In wound healing, the experimental animal model showed increased wound-size reduction in the CChF (Crimean–Congo hemorrhagic fever, a viral disease)-treated rats (96.25%) when compared to control rats (33.75%), followed by CF (cystic fibrosis) treated rats (65%) and ChF (chronic heart failure) (55%) (Ramasamy and Shanmugam, 2015). Hepatoprotective effect: The chitosan from this species showed antioxidative and hepatoprotective effects against Carbon tetrachloride (CCl4)-induced liver toxicity in Wistar rats. Rats treated with chitosan of this species showed significantly decreased levels of activities relating to ALT (alanine

Marine Mollusks

transaminase) and AST (aspartate aminotransferase), total cholesterol, triglyceride and free fatty acid in plasma and tissue. The treatment with chitosan along with CCl4, however, showed a markedly increased level of hepatic and circulatory in SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase), and reduced glutathione, and it decreased the malondialdehyde level. It is also suggested that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic properties (Ramasamy et al., 2014). Antibacterial activity: The chitosan and phosphorylated chitosan from cuttlebone of this species showed antibacterial activity against human pathogenic bacteria (Grampositive: Streptococcus sp., Streptococcus pneumoniae, and Staphylococcus aureus and Gram-negative: E. coli, V. cholerae, V. alginolyticus, V. parahaemolyticus, P. aeruginosa, K. pneumoniae, Salmonella sp., and P. vulgaris) (Shanmugam et al., 2016). Antioxidant property: The chitosan prepared from the chitin of this species exhibited antioxidant activity of 50.68%–74.36% at 1–10 mg.ml(−1). It also showed reducing power of 0.28% at 1 mg.ml(−1). At 10 mg.ml(−1), the chitosan exhibited scavenging ability of 46.17%, on 1,1-diphenyl-2-picrylhydrazyl radicals, 23.38%–73.70% on superoxide radicals at 0.05–1.6 mg.ml(−1), and 18.34% to 62.39% (0.1–3.2 mg.ml(−1)) on hydroxyl radicals; whereas at 1 to 10 mg.ml(−1), the chelating ability on ferrous ions was calculated as 49.74%–73.59%. Based on the potential antioxidant activity, scavenging ability on hydroxyl radicals, and chelating abilities on ferrous ions, it can be concluded that the chitosan from the cuttlebone of this species may not only be used as a potent natural antioxidant but also as a possible food quality enhancer ingredient in the pharmaceutical industry (Ramasamy et al., 2014).

Sepia officinalis (Linnaeus, 1758)

Order: SepiidaFamily: Sepiidae Common name: Common cuttlefish, European common cuttlefish Distribution: Eastern Atlantic and the Mediterranean: From the Shetlands and southern Norway (stray in the Baltic Sea), south to the Mediterranean Sea to northwestern Africa Ecology: It is a neritic, demersal species found in subtidal zones to depths of 200 m, generally over sandy-muddy substrates; it can tolerate brackish water conditions.

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Description: It has eight arms and two tentacles. Tentacular club of this species has five or six suckers in each transverse row, the median ones moderately enlarged. Left arm IV is hectocotylized, and its cuttlebone is rounded anteriorly and posteriorly. It is one of the largest and best-known cuttlefish species. It grows to 49 cm in mantle length (not including the head and the arms) and 4 kg in weight. Life span of this species is 1–2 years. Biology Food and feeding: In this species, the tentacles are shot out quickly to capture prey, and the arms are used to hold and move the prey around once it is caught. They have a parrotlike beak and a radula to tear and rasp their prey, which includes crustaceans and small fish. Reproduction: In this species, males attract females with a display of colors produced using their bioluminescence. It is gonochoristic. It reproduces sexually through external fertilization. The male and female line up head to head, and the male transfers spermatophores by means of the hectocotylus. The female stores the eggs in a sac/pouch just below her mouth. Spawning is in spring. Each female will lay several hundred eggs over a period of a few days. Shortly after a female lays her eggs, she dies, implying that reproduction only occurs once during the life cycle. Depending on water temperature, hatching occurs up to 2 months after the eggs are laid. The offspring hatch as miniature adults (6–9 mm). Adulthood occurs within 18–22 months, and in ideal conditions, they will mature within their first winter (Anon., https​://cu​ttlef​ ishse​piida​.weeb​ly.co​m /rep​roduc​tion-​and-l​ife-c​ycle.​html)​. Compound(s) and Activities Antibacterial activity: The methanol extract of this species showed antibacterial activity against V. cholera with inhibition dia less than 7 mm (Kanchana et al., 2014). Antioxidant, analgesic, and cytotoxic activities: The ink extract of this species showed inhibition of thiobarbituric acid–reactive substances (TBARAS) at all concentrations, with an IC50 value of 176.77 µg/ml; showed analgesic action by inhibiting acetic acid–induced writhing; exhibited significant antinociceptive actions in mice by increasing the latency period in the hot-plate test; significantly decreased the time of paw lickings in both early and late phases; and showed cytotoxic activities of HepG2 cell lines with an IC50 value of 67 µg/ml (Fahmy and Soliman, 2013). Anti-inflammatory activity: Mice treated with 200 mg/ kg of the ink extract (i.p.) of this species demonstrated its anti-inflammatory activity by inhibiting acetic acid–induced writhing (Ahmad et al., 2018). Therapeutic effect: The ink extract of this species showed a therapeutic effect against invasive pulmonary aspergillosis by reducing oxidative stress. The ink extract–treated mice showed 67.80% reduction in the pulmonary fungal burden. Further, treatment with ink extract for 1 and 3 days significantly decreased MDA (malondialdehyde) and increased

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GSH (glutathione) and SOD (superoxide dismutase) levels in the lung tissues as compared with the infected untreated group (Fahmy et al., 2014).

Sepia pharaonis (Ehrenberg, 1831)

Order: Sepiida Family: Sepiidae Common name: Pharaoh cuttlefish Distribution: Indo-West Pacific and Mediterranean Sea: From Red Sea to Japan and Australia Ecology: This benthic species is found over sand and seagrass beds of shallow coastal waters. It prefers a medium to high amount of sunlight for den location during the day. Further, it favors mud substrata during the day, but during the night it prefers sand or mud substrata equally. Its depth range is 0–130 m. Description: In this species, a distinct tiger-stripe pattern is seen on the dorsal side of the mantle. Tentacular club has big suckers, of which about six suckers in medial rows are much enlarged. Left ventral arm of male has 10–12 basal transverse series of normal suckers followed by 7 series of modified suckers. Cuttlebone is broad and thick and with a mid-ventral groove flattening anteriorly in striated area, inner cone forms a conspicuous yellowish flat ledge, and a sharp thick spine is present. Pharaoh cuttlefish often show a solid color when resting on a solid color background, alternating from a pale white to all dark brown. Additionally, they can show a mottled white and brown color, with a center circle of brown. It grows to 42 cm in mantle length and 5 kg in weight. Biology Food and feeding: It is an active predator, feeding on a variety of fish and crustaceans, and sometimes on other cephalopods. Reproduction: Females were dominant in the catch with a sex ratio of 1:1.24. Of the total, 40.2% males were immature, 43.6% mature, and 16.2% in spawning stage. Among females, 32% were immature, 30.6% mature, and 37.2% in spawning stage. All females were mature above 260 mm. The size at first maturity for females was estimated at 153 mm DML. In the present study, the maximum fecundity was 16,344 ova in November, and least was in September, with 369 ova. The ova diameter ranged from 2 to 8 mm. The GSI of females increased from September onwards and reached a primary peak in October; thereafter, there was decline till

Biology and Ecology of Pharmaceutical Marine Mollusks

December; then it increased to a secondary peak in February and thereafter there was a steep decline up to May (Figure 3). The observations indicate that the peak spawning season is from February to May and a minor spawning season occurs between October to December (Sundaram, 2014). Compound(s) and Activities Antioxidant activity: The methanolic extracts of this species registered significant total antioxidant activity, reducing capacity, and free-radical scavenging activity (DPPH) at a concentration of 100 μg/ml with 74.32%, 62.71%, and 81.25%, respectively. The hydrogen peroxide activity and the phenolic content was 82.19% and 86.34%, respectively. These findings indicate that S. pharaonis has a good source of natural antioxidants and could be useful for pharmaceutical applications (Ponnusamy et al., 2016). Anti-inflammatory activity: The liver oil of this species possesses anti-inflammatory activity. Carrageenan and formalin-induced paw edema of albino Sprague Dawley rats, when fed with 1% cuttlefish liver oil for 45 days, showed significant reduction (Ahmad et al., 2018). Others: The liver oil of this species has been reported to possess cardioprotective effects in rats (Pati et al., 2015). The outer skin of this species is a good source of acidsoluble collagen (ASC) (1.66%) and pepsin-soluble collagen (PSC) (3.93%), which would provide alternatives to mammalian collagen in food, cosmetics, and biomedical materials (Jayalakshmi et al., 2017).

Sepiella inermis (Van Hasselt, 1835)

Order: Sepiida Family: Sepiidae Common name: Spineless cuttlefish, glittering cuttlefish Distribution: Indo-West Pacific: From Indian Ocean to Indonesia and southern South China Sea Ecology: It is a benthic species with a depth range of 9–160 m. Description: S. inermis is a small-sized cuttlefish with narrow fins. Mantle has a pore at the posterior extremity, and the cuttlebone is without a spine. Shell is moderately small and rather narrowly ovate in outline; horny margin forms a characteristic thin, broad plate behind the calcareous portion and is highly glossy; and dorsal surface is finely granular and bears two shallow longitudinal grooves. Shell is chalky white, but the horny margin is pale brown and polished. Eyes are of moderate size. Mantle is conicocylindrical. Third and

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fourth pairs of arms are predominantly keeled. In males, the fourth arm on the left side is hectocotylized, and the basal portion of the arm does not have suckers. Total number of suckers on this arm (18–39) is less than the number of suckers on the other arms (37–82). Tentacles are elongate and rounded, bearing medium-sized tentacular clubs. Funnel is well developed. Jaws are horny and have well-developed cutting edges. Dorsal surface is grey brown or purple depending on the chromatophores present. There is a series of white spots on the dorsolateral surface of the mantle. Ventral surface is pale gray or pale brown. It attains a maximum mantle length of 12.5 cm. Biology Food and feeding: It feeds on a range of prey, including prawns, fish, stomatopods, crabs, and other crustaceans. Reproduction: Females generally attain the largest body sizes. Off India, individuals of this species mature and attain larger body sizes (up to 120 mm in mantle length). Spawning occurs throughout the year, with spawning peaks from June to September and from November to December in northeast India. The black, circular eggs are spawned singly and hatch in 12.6 days at 28˚C. The young are briefly planktonic before taking up the adult mode after several days (Anon., http:​// www​.iucn​redli​st.or​g/det​ails/​16250​0/0).​ Compound(s) and Activities Antifungal activity: The organic extracts of this species showed significant antifungal activity against Mucor racemosus and Penicillium expansum (Rajaganapathi et al., 2001). Anti-tubercular activity: When compared to chloroform extract, the methanol extract of this species was found to be more active and exhibited significant inhibitory effect against M. tuberculosis at the concentration of 64 µg/mL (Ravichandiran et al., 2013). Antimicrobial activity: The methanolic extract of this species showed antimicrobial activity as detailed below.

Methanolic Extract (%) 25

50

75

100

V. cholera

–

+

+

++

P. aeruginosa K. pneumoniae Staphylococcus aureus V. parahaemolyticus Streptococcus sp. S. pneumonia Salmonella sp.

+ + + – + – –

+ + + + + + –

+ ++ ++ + + + –

+ ++ ++ + ++ + +

E. coli

–

+

+

+

Source:  Ramasamy et al. (2011). –  No activity, + Weak activity (7–10 mm dia.), ++  Good activity (11–15 mm dia.), +++  Very good activity (above 16 mm dia.).

The MIC values for the bacterial strains V. cholerae, K. pneumonia, S. aureus, Streptococcus sp., S. pneumonia and E. coli were found to be 100, 80, 80, 80, 100, and 100 mg/ml, respectively (Ramasamy et al., 2011). Anti-inflammatory activity: The inner shell (Zhikang capsule [ZKC] component) of this species showed anti-inflammatory activity by suppressing TNFα, IFN-γ, IL-1β, and IL-12. Among the different doses, only the 680 mg/kg dose showed significant effect in all assays. Further, this component promoted antiinflammatory mediators (IL-4 and IL-10) (Ahmad et al., 2018). Angiotensin‐I converting enzyme inhibitory activity: The EtOAc‐MeOH extract of this species showed greater angiotensin‐converting enzyme‐I (ACE‐I) inhibitory activity with an IC90 value of 0.45 mg/mL (Chakraborty et al., 2017). Others: The outer skin of this species is a good source of ASC and PSC. The yield of ASC was low (0.58% on dryweight basis), whereas the yield of PSC was comparatively more (16.23% on dry-weight basis). The protein content of ASC and PSC was found to be 20.24% and 69.56%, respectively (on dry-weight basis). These collagens could provide alternatives to mammalian collagen in food, cosmetics, and biomedical materials (Shanmugam et al., 2012).

Octopus cyaneus (Gray, 1849)

Order: Octopoda Family: Octopodidae Common name: Big blue octopus, day octopus Distribution: Indo-Pacific: From Red Sea, East African coast, and Madagascar to southeastern Asia, Oceania, and as far as Hawaii Ecology: It is a shallow-water benthic species inhabiting coral reefs and found in a variety of substrata; dwells in lairs in coral bedrock, live and dead coral heads, and excavations in sand and rubble; in naturally-occurring holes on rocks or dens; depth range 30–120 m. Description: It is a large octopus. Mantle is round to oblong and is smooth-skinned (nonpapillose) with a few large tubercles. Arms are subequal in length, and one large cirrus and two smaller tubercles are seen over eye. Mantle is mottled and reticulate, and arms have purple-brown blotches. It attains a maximum length of 120 cm and weight of 6 kg. Biology Food and feeding: It is an opportunistic predator, pouncing on and capturing crabs. It feeds primarily on bivalves, gastropods, and xanthid crabs. It is an day-active species, with higher activity peaks at dusk and dawn.

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Behaviour: O. cyanea is adept at camouflage and not only can change color frequently, but can also change the patterns on and texture of its skin. It has been known to change its appearance 1,000 times in 7 hours. As it moves across the seabed, it makes changes in its coloring and appearance to match the substrate beneath. The color changes are instantaneous and made by chromatophores under direct control of the brain. Reproduction: It is gonochoric. Male and female adults usually die shortly after spawning and brooding, respectively. Males perform various displays to attract potential females for copulation. During copulation, the male grasps the female and inserts the hectocotylus into the female’s mantle cavity, where fertilization usually occurs. Embryos hatch into the planktonic stage and live for some time before they grow larger and take up a benthic existence as adults. Compound(s) and Activities Antibacterial activity: The methanolic extracts of this species showed antibacterial activity at 50 µl and 100 µl concentrations, and the values of inhibition zone for the different species are given below (Mohanraju et al., 2013).

Methanolic Extract 50 µl

100 µl

–

13 mm

E. coli K. pneumoniae Staphylococcus aureus

15 mm – 13 mm

17 mm 15 mm 15 mm

V. cholerae

15 mm

17 mm

B. subtilis

Source:  Mohanraju et al. (2013).

Octopus vulgaris (Cuvier, 1797)

Order: Octopoda Family: Octopodidae Common name: Common octopus Distribution: Circumglobal in temperate and tropical seas; eastern Atlantic: from Mediterranean Sea and southern coast

of England to Senegal in Africa; off the Azores, Canary Islands, and Cape Verde Islands; Western Atlantic Ecology: It is a reef-associated, oceanodromous species inhabiting rocky, sandy, and muddy bottoms of the coastline to the edge of the continental shelf; intertidal and subtidal areas; depth range 0–200 m. Description: It is a medium to large sized species and is chunky in appearance. Arms are stout and are of about equal length and thickness, and the dorsal pair of arms is slightly shorter. Shortened right arm III of males is hectocotylized by modification of tip into a very small, spoon-shaped ligula; and there are 7–11 gill lamellae on outer side of gill, including terminal lamella. It attains a maximum length of 1.3 m and weight of 10 kg. Biology Food and feeding: Its food consists of bivalves and crustaceans. It is able to change its color to blend in with its surroundings and is able to jump upon any unwary prey. Using its beak, it is able to break into the shells of shelled mollusks. It also uses venom to subdue its prey. Predator: Larvae and juveniles of this species are preyed upon by albacore (Thunnus alalunga) and adults by benthic fin fish. Behaviour: This species is known to undertake limited seasonal migrations, usually overwintering in deeper waters and occurring in shallower waters during summer. Reproduction: This species shows two spawning peaks per year throughout its distributional range. In the Mediterranean and the Inland Sea of Japan, the first occurs in April–May, corresponding to the group migrating in shore in spring (most important in the Mediterranean); and the second in October, corresponding to the group migrating in autumn (most important in Japan). In West Africa, around Cape Blanc, the first spawning peak occurs in May–June and the second (more important) in September. Females may produce between 120,000 and 400,000 eggs which they deposit in strings in crevices or holes, usually in shallow waters. Spawning may extend up to 1 month. During the brooding period (25–65 days), females stop feeding, and many die after the hatching of the larvae. The hatchlings are pelagic and settle to benthic life after about 40 days (Anon., http:​//www​.fao.​org/f​isher​y/spe​ cies/​3571/​en). Compound(s) and Activities Antifungal activity: The ink samples of this species showed antifungal activity (Datta et al., 2015). Antibacterial activity: The eggs of this species have been reported to release polypeptides, sexual pheromones, and AMPs that possess antimicrobial activity. Further, the methanolic acid extract of these hemocytes of its blood showed bactericidal activity (Troncone et al., 2012). Others: The boiled or roasted flesh of this species is believed to cure many gynecological diseases and conditions (Ahmad et al., 2018).

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Amphioctopus aegina (Gray, 1849) (=Octopus aegina)

Class: Cephalopoda Order: Octopoda  Family: Octopodidae Common name: Sandbird octopus Distribution: Indo-West Pacific: From Mozambique to Red Sea and Japan Ecology: It is found in sand and muddy sand areas. This benthic species is solitary with crepuscular (active primarily during twilight) behavior. Description: Animals are brownish green dorsally and pale white ventrally. Dorsal surfaces of the mantle, head, and arms are sculptured, with regular round patches with distinct grooves. A pale longitudinal stripe is seen along dorsal midline. A cream, narrow transverse head bar is present between the eyes. Transverse pairs of white spots are present on the dorsal mantle, just anterior to the mid-point of the mantle. Skin is with regular round patches and grooves. Mantle is elongate and ovoid and is covered with small tubercles or fine papillae. Head is small. Eyes are prominent and moderate in size. Single large cirrus is present at the base of each eye. Arms are short to moderate, two to three times the mantle length. Right third arm of males is hectocotylized. Suckers are biseria and l, normal arms are with 90–180 suckers. Two or three large suckers are present on the II and III arms of the males. Dark chromatophores are present at the base of each sucker. Hectocotylized arm has 58–79 suckers. It grows to a maximum length of 10 cm and a weight of 400 g. It is a commercial species. Biology Food and feeding: It can feed by probing its arms down holes in the mud to catch shrimp and fish. Reproduction: In this species, the ratios of males to females increased consistently with respect to weight. Weight at first maturity was 79 g for females and 41 g for males. Maturation and spawning occurred all year round, with a peak during October and another peak during January–February. The average relative fecundity was estimated at 68–83%, and the average number of oocytes per gram of ovary was 488–539 (Ignatius et al., 2011). Compound(s) and Activities Antibacterial activity: The extract of this species showed antibacterial activity against V. cholera (inhibition zone, 12 mm); V. parahaemolyticus (28 mm); V. anguillarum (25 mm); V. harveyi and V. alginolyticus (21 mm); and Vibrio sclintis (18 mm) (Monolisha et al., 2013).

Paroctopus limaculatus (Authority, not known) Image not available Order: Octopoda Family: Octopodidae Common name: Not known Distribution: Northeastern Pacific Ocean: off Mexico and Gulf of California; western Atlantic Ocean: Caribbean Sea; Gulf of Mexico Ecology: Not reported Description: These animals are small-bodied, short-mantled, pouchlike octopuses with short, stocky arms which are two or three times the length of the mantle. Males have one to three enlarged suckers on each arm, with their right third arm being hectocotylized and shorter than its opposite arm. One to three enlarged suckers are seen on all arms of males only. Ligula is of medium size with a short calamus. Their gills have six to eight lamellae per outer demibranch. Biology Food and feeding: Not reported. Reproduction: It lays small to medium-sized eggs which are on very short stalks and are attached singly in small clusters within the empty shells of gastropods and bivalves. Compound(s) and Activities Antimutagenicity: The antimutagenic compounds of the muscle extracts of this species showed an inhibitory effect on the mutagenicity of 500 ng of AFB1 (Aflatoxin B1, the most potent natural carcinogen) for both tester strains. Among the RA, RB, and RC fractions, RB fraction achieved the greater inhibition (>76% for both tester strains) of the mutagenicity of induced by 500 ng AFB1. Further, another fraction of RB, viz. RB21, inhibited the mutagenic potential of AFB1 in more than 95% and 89% for TA98 and TA100 tester strains, respectively (Moreno-Félix et al., 2013). Antiproliferative activity: All the RA, RB, and RC fractions of the lipidic extract of this species showed antiproliferative activity on the murine cancer cell line M12.C3.F6 (B-cell lymphoma) in a concentration-dependent manner. However, only fractions RA and RC were able to inhibit the cellular proliferation beyond 50% at the lowest doses tested (12.5 and 25 μg/mL). The highest level of cellular proliferation inhibition was observed for fraction RC (about 90% for the secondlowest dose tested (25 μg/mL). Fractions RC1 and RC2 were able to inhibit cellular proliferation in more than 50% at the highest dose tested (100 μg/mL) (Moreno-Félix et al., 2013). Antimutagenic, antiproliferative, and antioxidant effects: The hexanic extract of this species showed the highest antimutagenic and antiproliverative activities, inhibiting 80% and 43% of mutagenicity induced by AFB1 for TA98 and TA100, respectively, and showing a high antiproliferative activity at 200 and 100 µg/mL. However, when the antioxidant activity was evaluated at a concentration of 50 mg/mL, the methanolic fraction exerted inhibition of 98% and 96% ABTS and DPPH radicals, respectively (Cruz-Ramírez et al., 2015).

References Abdulazim, A., M. Hä drich, M. Montani, and N. Semmo, 2012. Acute hepatitis induced by lyprinol, the lipid extract of the green-lipped mussel (Perna canaliculus ), in a patient with polyarthrosis. Case Reports in Hepatology , 2012: 135146, 2 p. Afsar, N., and G. Siddiqui, 2013. Report of imposex syndrome in Thais tissoti  (Neogastropoda) from Vicinity of Karachi Port, Pakistan. Pakistan Journal of Zoology , 45: 1472– 1475. Agrawal, S., S. Chaugule, S. More, G. Rane, and M. Indap, 2017. Methanolic extract of Euchelus asper  exhibits in-ovo antiangiogenic and in vitro anti-proliferative activities. Biological Research , 50: 41, 12 p. Ahmad, T.B., L. Liuc, M. Kotiw, and K. Benkendorf, 2018. Review of anti-inflammatory, immune-modulatory and wound healing properties of molluscs. Journal of Ethnopharmacology , 210: 156– 178. Ajithkumar, P., N.S. Jeganathan, K. Balamurugan, R. Manvalan, and K. Radha, 2012. Evaluation of anti-ulcer activity of Villorita cyprinoides  extract (black water clams) against immobilization stress induced ulcer in albino rats. Journal of Pharmaceutical Research and Opinion , 2: 55– 57. Alam, M., G.E. Martin, A.S. Zektzer, A.J. Weinheimer, R. Sanduja, and M.A. Ghuman, 1993. Planaxool: A novel cytotoxic cembranoid from the mollusk Planaxis sulcatus . Journal of Natural Products , 56: 774– 779. Alam, M., and R.H. Thomson, 1997. Handbook of Natural Products from Marine Invertebrates , Part 1-Science, Boca Raton, CRC Press, 288 p. Aldairi, A.F., O.D. Ogundipe, and D.A. Pye, 2018. Antiproliferative activity of glycosaminoglycan-like polysaccharides derived from marine molluscs. Marine Drugs , 16: 63, 16 p. Alemá n, A., B. Gimé nez, E. Pé rez-Santin, M. Gó mez-Guillé n, and P. Montero, 2011a. Contribution of Leu and Hyp residues to antioxidant and ACE-inhibitory activities of peptide sequences isolated from squid gelatin hydrolysate. Food Chemistry , 125: 334– 341. Alemá n, A., E. Pé rez-Santí n, S. Bordenave-Juchereau, I. Arnaudin, M.C. Gó mez-Guillé n, and P. Montero, 2011b. Squid gelatin hydrolysates with antihypertensive, anticancer and antioxidant activity. Food Research International , 44: 1044– 1051. Alfaro, A.C., A.G. Jeffs, and S.H. Hooker, 2001. Reproductive behavior of the green-lipped mussel, Perna canaliculus , in northern New Zealand. Bulletin of Marine Science , 69: 1095– 1108. Ameri, A., M.R. Shushizadeh, S.M.B. Nabavi, F. Espere, and A.Z. Ahmady, 2017. Antibacterial valuation and biochemical characterization of Thais savignyi  gastropod extracts from the Persian Gulf. Jundishapur Journal of Natural Pharmaceutical Products , 12: e13942. Amiza, M.A., H.A. Liyana, and Z.H. Madridge, 2017. Optimization of enzymatic protein hydrolysis conditions to obtain maximum angiotensin-iconverting enzyme (ACE) inhibitory activity from angel wing clam (Pholas orientalis ) meat. Journal of Food Technology , 2: 65– 73. Amornrut, C., T.T.T. Imanari, E.R. Woo, H. Park, R. Linhardt, S.J. Wu, and Y.S. Kim, 1999. A new sulfated beta-galactan from clams with anti-HIV activity. Carbohydrate Research , 321: 121– 127. Anand, T.P., C. Chellaram, S. Kumaran, and C.F. Shanthini, 2010. Biochemical composition and antioxidant activity of Pleuroploca trapezium  meat. Journal of Chemical and Pharmaceutical Research , 2: 526– 535.

Anand, T.P., and J.K.P. Edward, 2002. Antimicrobial activity in the tissue extracts of five secies of cowries, Cypraea (Mollusca: Gastropoda) and an ascidian Didemnum psammathodes  (Tunicata: Didemnida). Indian Journal of Marine Sciences , 3: 239– 242. Anderson, R.S., and A.E. Beaven, 2001. Antibacterial activities of oyster (Crassostrea virginica ) and mussel (Mytilus edulis  and Geukensia demissa ) plasma. Aquatic Living Resources , 14: 343– 349. Andrianasolo, E.H., L. Haramaty, K.L. McPhail, E. White, C. Vetriani, P. Falkowski, and R. Lutz, 2011. Bathymodiolamides A and B, ceramide derivatives from a deep-sea hydrothermal vent invertebrate mussel, Bathymodiolus thermophilus . Journal of Natural Products , 74: 842– 846. Annamalai, N., R. Anburaj, S. Jayalakshmi, and R. Thavasi, 2007. Antibacterial activities of green mussel (Perna viridis ) and edible oyster (Crassostrea madrasensis ). Research Journal of Microbiology , 2: 978– 982. Anon. CABI. https://www.cabi.org/isc/datasheet/66682. Anon. DORIS. http:​//dor​is.ff​essm.​fr/Es​peces​/ Thur​idill​a-hop​ei-Th​ uridi​lle-d​e-Hop​e-955​. Anon. Haliotis rufescens, Animal Diversity web. https​://an​imald​ ivers​ity.o​rg/ac​count​s/Hal​iotis​_ rufe​scens​/. Anon. http:​//www​.sigm​aaldr​ich.c​om/ca​talog​/prod​uct/s​igma/​g2174​ ?lang​=en&r​egion​=IN. Anon. https://www.google.com/patents/US8436141. Anon. https​://ww​w.the​freel​ibrar​y.com​/ Pote​ntial​+anti​m icro​bial+​ activ​ity+o​f+mar​ine+m​ollus​cs+fr​om+tu​ticor​in%2c​..-a0​13310​ 8179. Anon. http:​//sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​64373​/16/1​ 6_cha​pter%​2011.​pdf. Anon. http:​//ani​maldi​versi​ty.or​g/acc​ounts​/Cras​sostr​ea_vi​rgini​ca/. Anon. http:​//bio​web.u​wlax.​edu/b​io203​/f201​3/yur​k_dev​i/rep​roduc​tion.​ htm. Anon. http:​//dor​is.ff​essm.​fr/Es​peces​/Ocen​ebra-​erina​ceus-​Corma​illot​ -1429​. Anon. http:​//dor​is.ff​essm.​fr/Es​peces​/ Phil​inops​is-de​picta​-Agla​ja-ch​ arnue​-1117​. Anon. http:​//dor​is.ff​essm.​fr/Es​peces​/ Pleu​robra​nchus​-fors​kalii​-Pleu​ robra​nche-​de-Fo​rskal​-1310​. Anon. http:​//epr​ints.​cmfri​.org.​in/16​91/1/​Mahad​evan_​213-2​18.pd​f. Anon. http:​//epr​ints.​cmfri​.org.​in/68​95/1/​033-C​URREN​T_SCI​ENCE-​ 3.pdf​. Anon. http:​//inv​asion​s.si.​edu/n​emesi​s/jtm​d/Spe​ciesS​ummar​y.jsp​?taxo​ n=Myt​ilus%​20cor​uscus​. Anon. http:​//sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​13521​0/12/​ 12_ch​apter​%207.​pdf. Anon. http:​//sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​36803​/13/1​ 3_cha​pter%​207.p​df. Anon. http:​//sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​38427​ /6/06​_chap​ter%2​01.pd​f. Anon. http:​//wav​es-va​gues.​dfo-m​po.gc​.ca/L​ibrar​y/264​626.p​df. Anon. http:​//www​.cies​m.org​/atla​s/Sac​costr​eacuc​ullat​a.htm​l. Anon. http:​//www​.fao.​org/d​ocrep​/fiel​d/003​/AB73​6E/AB​736E0​5.htm​. Anon. http:​//www​.fao.​org/f​i sher​y/cul​tured​speci​es/Os​trea_​eduli​s/en. Anon. http:​//www​.fao.​org/f​i sher​y/spe​cies/​3571/​en. Anon. http://www.fegi.ru/prim/sea/m_dvu28.htm. Anon. http:​//www​.iucn​redli​st.or​g/det​ails/​16250​0/0. Anon. http:​//www​.iucn​redli​st.or​g/det​ails/​16259​4/0. 175

176 Anon. http:​//www​.iucn​redli​st.or​g/det​ails/​16266​6/0. Anon. http://www.uniprot.org/uniprot/P58990. Anon. http://www.uniprot.org/uniprot/P60207. Anon. http://www.uniprot.org/uniprot/P69757. Anon. http://www.uniprot.org/uniprot/P81612. Anon. http://www.uniprot.org/uniprot/P81613. Anon. http://www.uniprot.org/uniprot/Q7Z096. Anon. http://www.uniprot.org/uniprot/Q9Y0B1. Anon. http://www.uniprot.org/uniprot/U3KTS1. Anon. https​://an​imald​ivers​ity.o​rg/ac​count​s/Hal​iotis​_ rufe​scens​/. Anon. https​://an​imald​ivers​ity.o​rg/ac​count​s/Pin​ctada​_marg​a riti​fera/​. Anon. https​://cu​ttlef​i shse​piida​.weeb​ly.co​m /rep​roduc​tion-​and-l​ife-c​ ycle.​html. Anon. https​://sa​nctua​rysim​on.or​g/dbt​ools/​speci​es-da​tabas​e/id/​832/m​ onter​eina/​nobil​is/no​ble-s​ea-le​mon. Anon. https​://ww​w.dpi​.nsw.​gov.a​u/__d​ata/a​ssets​/pdf_​file/​0009/​37585​ 8/Bla​cklip​Abalo​ne.pd​f. Anon. https​://ww​w.gbr​i.org​.au/S​pecie​s/Pla​naxis​sulca​tus.a​spx?P​ageCo​ ntent​ID=22​25. Anon. https​://ww​w.sms​.si.e​du/ir​lspec​/ Merc​en_ca​mpec.​htm. Anon. https​://ww​w.sms​.si.e​du/ir​lspec​/Stro​mbus_​gigas​.htm. Anon. http:​//sho​dhgan​ga.in​flibn​et.ac​.in/b​itstr​eam/1​0603/​38427​/7/07​ _chap​ter%2​02.pd​f. Anon. Indian River Lagoon Species Inventory. https​://ww​w.sms​.si.e​ du/ir​lspec​/ Merc​en_me​rcen.​htm. Anon. Indian River Lagoon Species Inventory. http:​//www​.sms.​si.ed​ u/irl​spec/​perna ​_viri​dis.h​tm. Anon. Littorina littorea, Species Information. BIOTIC – Biological Traits Information Catalogue, https://www.marlin.ac.uk/ biotic/browse.php?sp=4202. Appleton, D.R., M.A. Sewell, M.V. Berridge, and B.R. Copp, 2002. A new biologically active malyngamide from a New Zealand collection of the sea hare Bursatella leachii . Journal of Natural Products , 65: 630– 631. Arancibia, S., C. Espinoza, F. Salazar, M.D. Campo, R. Tampe, T. Zhong, P. De Ioannes, B. Moltedo, J. Ferreira, E.C. Lavelle, A. Manubens, A.E. De Ioannes, and M.I. Becker, 2014. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata  promotes potent anti-tumor activity in melanoma. PLoS One , 9: e87240. Argente, F.A.T., and A.S. Ilano, 2015. Susceptibility of some pathogenic microbes to soft tissue extract of the mud clam, Polymesoda expansa  (Bivalvia: Corbiculidae). The Experiment , 30: 1984– 1990. Arumugasamy, K., and R. Cyril, 2017. Cytotoxicity, antibacterial and antioxidant activities of the tissue extracts of marine gastropod Hemifusus pugilinus  (Born, 1778). Journal of Chemical and Pharmaceutical Research , 9: 267– 274. Arun, A.U., 2009. Gametogenic cycle in Villorita cyprinoides  and the influence of salinity. Aquaculture, Aquarium, Conservation & Legislation International Journal of the Bioflux Society  , 433–  447. http:​//www​.biof​l ux.c​om.ro​/docs​ /2009​.2.43​3-447​.pdf. Ashour, M., R. Edrada, R. Ebel, V. Wray, W. Wä tjen, K. Padmakumar, W.E.G. Mü ller, W.H. Lin, and P. Proksch, 2006. Kahalalide derivatives from the Indian sacoglossan mollusk Elysia grandifolia . Journal of Natural Products , 69: 1547– 1553. Atta-ur-Rahman, 2012. Studies in Natural Products Chemistry . Elsevier, 415 p. Attaway, D.H., and O.R. Zaborsky, 1993. Pharmaceutical and Bioactive Natural Products . Springer Science+Business Media, NY. Babar, A.G., A. Pande, and B.G. Kulkarni, 2012. Bioactive potential of some intertidal molluscs collected from Mumbai coast, west coast of India. Asian Pacific Journal of Tropical Biomedicine , 2: S1060– S1063.

References Babar, A.G., A. Pande, and B.G. Kulkarni, 2016. Antifungal activity and investigation of bioactive compounds of marine intertidal bivalve Gafrarium divaricatum  from west coast of India. International Journal of Pure & Applied Bioscience , 4: 211– 217. Badiu, D.L., R. Luque, E. Dumitrescu, A. Craciun, and D. Dinca, 2010. Amino acids from Mytilus galloprovincialis  (L.) and Rapana venosa  molluscs accelerate skin wounds healing via enhancement of dermal and epidermal neoformation. The Protein Journal , 29: 81– 92. Barbieri, E., K. Barry, A. Child, N. Wainwright, 1997. Antimicrobial activity in the microbial community of the accessory nidamental gland and egg cases of Loligo pealei  (Cephalopoda: Loliginidae). Biological Bulletin , 193: 275– 276. Behzadi, S., K. Parivar, and P. Roustaian, 1997. Gonad cycle of pearl oyster, Pinctada fucata  (Gould) in northeast Persian Gulf, Iran. Journal of the Shellfish Research , 16: 129– 135. Belcheva, N.N., N.V. Dovzhenko, A.A. Istomina, A.F. Zhukovskaya, and S.P. Kukla, 2016. The antioxidant system of the Gray’ s mussel Crenomytilus grayanus  (Dunker, 1853) and the Japanese scallop Mizuhopecten yessoensis  (Jay, 1857) (Mollusca: Bivalvia). Russian Journal of Marine Biology , 42: 489– 494. Belda, C.A., and A.G.C. Del Norte, 1988. Notes on the induced spawning and larval rearing of the Asian moon scallop, Amusium pleuronectes  (Linné  ), in the laboratory. Aquaculture , 72: 173– 179. Benkendorff, K., 2010. Molluscan biological and chemical diversity: Secondary metabolites and medicinal resources produced by marine molluscs. Biological Reviews , 85: 757– 775. Benkendorff, K., 2014. Chemical diversity in molluscan communities: From natural products to chemical ecology. In: A.D. Cosmo and W. Winlow (eds), Neuroecology and Neuroethology in Molluscs: The Interface between Behaviour and Environment . Nova Science Publishers, New York, pp. 13– 41. Benkendorff, K., D. Rudd, B.D. Nongmaithem, L. Liu, F. Young, V. Edwards, C. Avila, and C.A. Abbott, 2015. Are the traditional medical uses of Muricidae molluscs substantiated by their pharmacological properties and bioactive compounds? Marine Drugs , 13: 5237– 5275. Blunt, J.W., B.R. Copp, R.A. Keyzers, M.H.G. Munroa, and M.R. Prinsepd, 2016. Marine natural products. Natural Product Reports , 33: 382– 431. Blunt, J.W., B.R. Copp, M.H.G. Munro, P.T. Northcote, and M.R. Prinsep, 2006. Marine natural products. Natural Product Reports , 23: 26–78. Borquaye, L.S., G. Darko, M.K. Laryea, V.R.R. Boateng, and E.N. Gasu, L. Giamperi, 2017. Anti-inflammatory activities of extracts from Oliva sp., Patella rustica , and Littorina littorea  collected from Ghana’ s coastal shorelines. Cogent Biology , 3: 1364063. Borquaye, L.S., G. Darko, and E. Ocansey, Ankomah, E. 2015. Antimicrobial and antioxidant properties of the crude peptide extracts of Galatea paradoxa  and Patella rustica . SpringerPlus , 4: 500. DOI: 10.1186/s40064-015-1266-2. Brien, S., P. Prescott, B. Coghlan, N. Bashir, and G. Lewith, 2008. Systematic review of nutritional supplement Perna canaliculus (green-lipped mussel) in the treatment of osetoarthritis. QJM, 101: 167–179. Bulaj, G., P.J. West, J.E. Garrett, M. Watkins, M. Zhang, R.S. Norton, B.J. Smith, D. Yoshikami, and B.M. Olivera, 2005. Novel conotoxins from Conus striatus  and Conus kinoshitai  selectively block TTX-resistant sodium channels. Biochemistry , 44: 7259– 7265.

References Cahyani, R.T., S. Purwaningsih, and A. Azrifitria, 2015. Antidiabetic potential and secondary metabolites screening of mangrove gastropod Cerithidea obtusa . Journal of Coastal Life Medicine , 3: 356– 360. Carbone, M., M.C. Ciavatta, G.D. Rinaldis, F. Castelluccio, E. Mollo, and M. Gavagnin, 2014. Identification of thuridillinrelated aldehydes from Mediterranean sacoglossan mollusc, Thuridilla hopei . Tetrahydron , 70: 3770– 3773. Carbone, M., C. Irace, F. Costagliola, F. Castelluccio, G. Villani, G. Calado, V. Padula, G. Cimino, J.L. Cervera, R. Santamaria, and M. Gavagnin, 2010. A new cytotoxic tambjamine alkaloid from the Azorean nudibranch Tambja ceutae . Bioorganic & Medicinal Chemistry Letters , 20: 2668– 2670. Carriel-Gomes, M.C., J.M. Kratz, V.D.M. Mü  l ler, C.R.M. Barardi, and C.M.O. Simõ es, 2006. Evaluation of antiviral activity in hemolymph from oysters Crassostrea rhizophorae  and Crassostrea gigas . Aquatic Living Resources , 19: 189– 193. Caughey, D.E., R.R. Grigor, E.B. Caughey, P. Young, P.J. Gow, and A.W. Stewart, 1983. Perna canaliculus  in the treatment of rheumatoid arthritis. European Journal of Rheumatology and Inflammation , 6, 197– 200. Cavalcanti, B.C., V.N. Hé  lio Jú  nior, M.H.R. Seleghim, R.G.S. Berlinck, G.M.A. Cunha, M.O. Moraes, and C. Pessoa, 2008. Cytotoxic and genotoxic effects of tambjamine D, an alkaloid isolated from the nudibranch Tambja eliora , on Chinese hamster lung fibroblasts. Chemico-Biological Interactions , 174: 155– 162. Chakraborty, K., M. Joy, V.K. Raola, F. Makkar, 2017. Angiotensin‐ I converting enzyme inhibitory activities of common edible cephalopods and their antioxidative effects using different in vitro models. Journal of Food Chemistry , 41: e12268. Changgui, D., 1996. Experimental studies on hypoglycemia and hypolipid effects of hydroly-sate of Arca subcrenata . Chinese Journal of Marine Drugs , 15: 13– 15. Chanrachkij, I., 2013. Undulated Surf Clam (Paphia spp.) Dredge Fishing of Thailand 1— Overview . Southeast Asian Fisheries Development Center. Chatterji, A., Z.A. Ansari, B.S. Ingole, M.A. Bichurina, M. Sovetova, and Y.A. Boikov, 2002. Indian marine bivalves: Potential source of antiviral drugs. Current Science , 82: 1279– 1282. Chelladurai, C., J. Mohanraj, and I. Vijayakumar, 2015. Antibiogram of coral reef associated molluscs from Tuticorin coast, Gulf of Mannar, India. Indian Journal of Geo-Marine Science , 44: 1112– 1119. Chellaram, C., and J.K.P. Edward, 2009a. Anti-inflammatory potential of coral reef associated gastropod, Drupa margariticola . Indian Journal of Science and Technology , 2: 75– 77. Chellaram, C., and J.K.P. Edward, 2009b. Anti-nociceptive assets of coral associated gastropod, Drupa margariticola . International Journal of Pharmacology , 5: 236– 239. Chellaram, C., and A.A. John, 2014. Isolation of bioactive compounds from marine mollusk against human pathogens. Proceedings of International Conference on Science Engineering and Management Research (ICSEMR) , Chennai. Chellaram, C., T.P. Anand, G. Kuberan, A.A. John, G. Priya, and B.A. Kumar, 2012. Anti-inflammatory and analgesic effects of coral reef associated gastropod, Trochus tentorium  from Tuticorin coastal waters, southeastern India. African Journal of Biotechnology , 11: 14621– 14626. Chellaram, C., K.M.E. Gnanambal, and J.K.P. Edward, 2005. Isolation and screening of mucus-associated bacteria of the gastropod, Drupa margariticola  for antagonistic activity. Journal of the Marine Biological Association of India , 47: 154– 159.

177 Chellaram, C., K. Gnanambal, M. Elizabeth, and E.J.K. Patterson, 2004. Antibacterial activity of the winged oyster Pteria chinensis  (Pterioida: Pteridae). Indian Journal of Marine Sciences , 33: 369– 372. Chen, H., X. Chu, C. Yan, X. Chen, M. Sun, Y. Wang, C. Wang, and W. Yu, 2007. Polypeptide from Chlamys farreri  attenuates murine thymocytes damage induced by ultraviolet B. Acta Pharmacologica Sinica, 28: 1665– 1670. Chen, X., Y. Han, S. Zhan, C. Wang, and S. Chen, 2015. Tegillarca granosa  extract haishengsu induces apoptosis in human hepatocellular carcinoma cell line BEL-7402 via fas-signaling pathways. Cell Biochemistry and Biophysics , 71: 837– 844. Chen, L., L. Song, T. Li, J. Zhu, J. Xu, Q. Zheng, and R. Yu, 2013. A new antiproliferative and antioxidant peptide isolated from Arca subcrenata . Marine Drugs , 11: 1800– 1814. Cheng, L.S., L.D. Tao, G.J. Long, H.B. Yong, Z.C. Hua, H.J. Ming, and Z. Li, 2009. Lipid components of Ostrea rivularis , Paphia undulata  and Pinctada martensii . Journal of Fishery Sciences of China , 33: 666– 671. Cheong, S.H., J.W. Hwang, S.H. Lee, Y.S. Kim, E.J. Sim, E.K. Kim, B.I. You, S.H. Lee, D.J. Park, C.B. Ahn, B.T. Jeon, S.H. Moon, and P.J. Park, 2015. Anti-inflammatory effect of short neck clam (Tapes philippinarum ) water extract containing taurine in zebrafish model. Advances in Experimental Medicine and Biology , 803: 819– 831. Chernikov, O.V., W. Wong, L. Li, I.V. Chikalovets, V.I. Molchanova, S. Wu, J. Liao, and K. Hua, 2017. A GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus  modulates immune response in macrophages and in mice. Scientific Reports , 7: 6315. Chikalovets, I.V., O.V. Chernikova, M.V. Pivkina, V.I. Molchanovaa, A.P. Litovchenkob, W. Lic, and P.A. Lukyanova, 2015. A lectin with antifungal activity from the mussel Crenomytilus grayanus . Fish and Shellfish Immunology , 42: 503– 507. Ciavatta, M.L., E. Manzo, E. Mollo, C.A. Mattia, C. Tedesco, C. Irace, Y.W. Guo, X.B. Li, G. Cimono, and M. Gavagnin, 2011. Tritoniopsins A-D, cladiellane-based diterpenes from the South China Sea nudibranch Tritoniopsis elegans and its prey Cladiella krempfi. Journal of Natural Products, 74: 1902–1907. Ciavatta, M.L., P. Devi, M. Carbone, V. Mathieu, R. Kiss, A. Casapullo, and M. Gavagnin, 2016. Kahalalide F analogues from the mucous secretion of Indian sacoglossan mollusk Elysia ornata . Tetrahedron , 72: 625– 631. Ciavatta, M.L., F. Lefranc, M. Carbone, E. Mollo, M. Gavagnin, T. Betancourt, R. Dasari, A. Kornienko, and R. Kiss, 2017. Marine mollusk‐ derived agents with antiproliferative activity as promising anticancer agents to overcome chemotherapy resistance. Medicinal Research Reviews , 37: 702– 801. Ciminiello, P., C. Dell’  Aversano, E. Fattorusso, M. Forino, S. Magno, A. Ianaro, and M.D. Rosa, 2001. Oxazinin‐ 1, ‐ 2 and ‐ 3 — A novel toxic compound and its analogues from the digestive glands of Mytilus galloprovincialis . European Journal of Organic Chemistry , 2001: 49– 53. Ciminiello, P., C. Dell’  Aversano, E. Fattorusso, M. Forino, S. Magno, F.U. Santelia, V.I. Moutsos, E.N. Pitsinos, and E.A. Couladouros, 2006. Oxazinins from toxic mussels: Isolation of a novel oxazinin and reassignment of the C-2 configuration of oxazinin-1 and -2 on the basis of synthetic models. Tetrahedron , 62: 7738– 7743. Cimino, G., S. De Rosa, S. De Stefano, and G. Sodano, 1986. Marine natural products: New results from Mediterranean invertebrates. Pure and Applied Chemistry , 58: 375– 386.

178 Cimino, G., G. Sodano, A. Spinella, and E. Trivellone, 1985. Aglajne-1, a polypropionate metabolite from the opisthobranch mollusc Aglaja depicta  : Determination of carbon–  carbon connectivity via long-range 1H-13C couplings. Tetrahedron Letters , 26: 3389– 3392. Conus radiatus— http://www.uniprot.org/uniprot/P58990. Conus radiatus— http://www.uniprot.org/uniprot/Q7Z096. Conus radiatus— Wikipedia. Conus stercusmuscarum—  Delta-conotoxin-like SmVIA (http:// www.uniprot.org/uniprot/P69757). Conus stercusmuscarum— http://www.uniprot.org/uniprot/P60207. Cruz-Ramí  rez, S., C. Ló  pez-Saiz, E. Rosas-Burgos, F. CincoMoroyoqui, C. Velá zquez, J. Herná ndez, A. Burgos-Herná ndez, 2015. Antimutagenic, antiproliferative, and antioxidant effects of extracts obtained from octopus (Paraoctopus limaculatus ). Food Science and Technology (Campinas) , 35: 722– 728. Cuadros, R., E.M. de Garcini, F. Wandosell, and J. Avila, 2000. The marine compound spisulosine, an inhibitor of cell proliferation, promoting the disassembly of actin stress fibers. Cancer Letters , 152: 23– 29. Cui, Q., H. Wang, and C. Yuan, 2014. The preliminary study on the antithrombotic mechanism of glycosaminoglycan from Mactra veneriformis . Blood Coagulation & Fibrinolysis , 25: 16– 19. Dang, V.T., K. Benkendorff, T. Green, and P. Speck, 2015. Marine snails and slugs: A great place to look for antiviral drugs. Journal of Virology , 89: 8114– 8118. Dang, V.T., K. Benkendorff, and P. Speck, 2011. In vitro antiviral activity against herpes simplex virus in the abalone Haliotis laevigata . Journal of General Virology , 92: 627– 637. Datta, D., S.N. Talapatra, and S. Swarnakar, 2015. Bioactive compounds from marine invertebrates for potential medicines— An overview. International Letters of Natural Sciences , 7: 42– 61. De Zoysa, M., C. Nikapitiya, I. WhangI, J.S. Lee, and J. Lee, 2009. Abhisin: A potential antimicrobial peptide derived from histone H2A of disk abalone (Haliotis discus discus ). Fish and Shellfish Immunology , 27: 639– 646. Dean, L.J., and M.R. Prinsep, 2017. The chemistry and chemical ecology of nudibranchs. Natural Product Reports , 34: 1359– 1390. Defer, D., N. Bourgougnon, and Y. Fleury, 2009. Screening for antibacterial and antiviral activities in three bivalve and two gastropod marine molluscs. Aquaculture , 293: 1– 7. Degiam, Z.D., and A.T. Abas, 2010. Antimicrobial activity of some crude marine Mollusca extracts against some human pathogenic bacteria. Thi-Qar Medical Journal , 4: 142– 147. Devi, P., and K. Revathi, 2015. The diversity of nudibranchs in Andaman Islands and screening of bioactive compounds from Plakobranchus ocellatus . International Journal of Advanced Research in Biological Sciences , 2: 280– 288. Dhinakaran, A., V. Sekar, G.V. Sethubathi, and J. Suriya, 2011. Antipathogenic activity of marine Gastropoda (Hemifusus pugilinus  ) from Pazhayar, South East Coast of India. International Journal of Environmental Sciences , 2: 536– 542. Diaz, J.H.J., R.D. Thilaga, and V. Sivakumar, 2015. In-vitro cytotoxic activity of squid and cuttlefish bone extract on Hep G2 cell line. International Journal of Pharmaceutical Sciences and Research, 6: 778–782. Diaz-Marrero, A., N. Issi, V. Canales, C. Chamy, A. San-Martin, D.J. Rovirosa, 2008. New diterpenes from the marine pulmonate Trimusculus peruvianus . Natural Product Research , 22: 1516– 1520. Dí az-Marrero, A.R., E. Dorta, M. Cueto, J. Rovirosa, A. SanMartí n, A. Loyola, and J. Darias, 2003. New polyhydroxylated steroids from the marine pulmonate Trimusculus peruvianus . Issue in Honor of Prof. R. Rossi and Prof. E. Rú veda, Archive for Organic Chemistry (ARKIVOC) , Arkat USA, 107– 117.

References Dietrich, C.P., J.F. de Paiva, C.T. Moraes, H.K. Takashi, M.A. Porcionatto, and H.B. Nader, 1985. Isolation and characterization of a heparin with high anticoagulant activity from Anomalocardia brasiliana . Biochimica et Biophysica Acta , 843: 1– 7. Diyabalanage, T., K.B. Iken, J.B. McClintock, C.D. Amsler, B.J. Baker, 2010. Palmadorins A– C, diterpene glycerides from the antarctic nudibranch Austrodoris kerguelenensis . Journal of Natural Products , 73: 416– 421. Dolashka, P., V. Moshtanska, V. Borisova, A. Dolashki, S. Stevanovic, T. Dimanov, and W. Voelter, 2011. Antimicrobial proline-rich peptides from the hemolymph of marine snail Rapana venosa . Peptides , 32: 1477– 1483. Duddu, S.K., T. Gurugubelli, K.G. Gandham, and A. Dogiparti, 2017. Antibacterial activity of the crude extract of a gastropod Cellana radiata  (Born, 1778) from the Visakhapatnam Coast, Andhra Pradesh, India. International Journal of Marine Science , 7: 125– 129. Duggan, P.J., and K.L. Tuck, 2015. Bioactive mimetics of conotoxins and other venom peptides. Toxins (Basel) , 7: 4175– 4198. Duran, A.C., A. Castro-Acedo, J.A. Arreola-Lizarraga, and J. Chavez-Villalba, 2013. Gametogenic cycle and condition index of the clam Chione fluctifraga  in Bahia San Jorge, Gulf of California, Mexico. Revista de Biologia Marina y Oceanografia , 48: 59– 72. Edwards, V., 1967. The effects of bioactive compounds from the marine mollusc Dicathais orbita  on human reproductive cells and human reproductive cancer cells. Ph.D. Thesis, Flinders University. Elhasni, K., M. Ghorbel, P. Vasconcelos, and O. Jarboui, 2010. Reproductive cycle and size at first sexual maturity of Hexaplex trunculus (Gastropoda: Muricidae) in the Gulf of Gabès (southern Tunisia). Invertebrate Reproduction & Development, 54: 213–225. El-Sorogy, A., A. El Kammar, A. Ziko, M. Aly, and H. Nour, 2013. Gastropod shells as pollution indicators, Red Sea coast, Egypt. Journal of African Earth Sciences , 87: 93– 99. Fahmy, S.R., and A.M. Soliman, 2013. In vitro antioxidant, analgesic and cytotoxic activities of Sepia officinalis  ink and Coelatura aegyptiaca  extracts. African Journal of Pharmacy and Pharmacology , 7: 1512– 1522. Fahmy, S.R., E.M. Ali, and N.S. Ahmed, 2014. Therapeutic effect of Sepia  ink extract against invasive pulmonary aspergillosis in mice. The Journal of Basic & Applied Zoology , 67: 196– 204. Faircloth, G., and M.C.C. Marchante, 2006. Kahalalide F and Es 285: Potent anticancer agents from marine molluscs. Progress in Molecular and Subcellular Biology , 43: 363– 379. Fan, H., J. Peng, M.T. Hamann, and J. Hu, 2008. Lamellarins and related pyrrole-derived alkaloids from marine organisms. Chemical Reviews , 108: 264– 287. FAO. http:​//www​.fao.​org/f​i sher​y/cul​tured​speci​es/My​tilus​_gall​o­prov​ incia​lis/e​n. FAO. http:​//www​.fao.​org/f​i sher​y/cul​tured​speci​es/Ru​ditap​es_ph​ilipp​ inaru​m /en. Faulkner, D.J., 2001. Marine natural products. Natural Product Reports , 18: 1– 49. Fisch, K.M., C. Hertzer, N. Bö h ringer, Z.G. Wuisan, D. Schillo, R. Bara, F. Kaligis, H. Wä gele, G.M. Kö nig, and T.F. Schä berle, 2017. The potential of Indonesian heterobranchs found around Bunaken Island for the production of bioactive compounds. Marine Drugs , 15: 384. DOI: 10.3390/md15120384, 45 p. Fontana, A., P. Cavaliere, S. Wahidulla, C.G. Naik, and G. Cimino, 2000. A new antitumor isoquinoline alkaloid from the marine nudibranch Jorunna funebris . Tetrahedron , 56: 7305– 7308.

References Forster, L.C., G.K. Pierens, A.M. White, K.L. Cheney, P. Dewapriya, R.J. Capon, and M.J. Garson, 2017. Cytotoxic spiroepoxide lactone and its putative biosynthetic precursor from Goniobranchus splendidus . ACS Omega , 2: 2672– 2677. Freites, L., N. Garcí a, L. Troccoli, A.N. Maeda-Martí nez, M.J. Ferná ndez-Reiriz, 2010. Influence of environmental variables and reproduction on the gonadal fatty acid profile of tropical scallop Nodipecten nodosus . Comparative Biochemistry and Physiology-Part B: Biochemistry and Molecular Biology , 157: 408– 414. Fukuyama, Y., C.M. Kodama, M. Ochi, K. Kataoka, and K. Shibata, 1998. Antimicrobial indolequinones from the mid-intestinal gland of the muricid gastropod Drupella fragum. Tetrahedron, 54: 10007-10016. Gal, Y.L., and R. Ulber, 2005. Marine Biotechnology II . Springer Science & Business Media-Nature, 261 p. Gao, J., and M.T. Hamann, 2011. Chemistry and biology of kahalalides. Chemical Reviews , 111: 3208– 3235. Garcí a, P.A., E. Valles, D. Dí ez, and M. Castro, 2018. Marine alkylpurines: A promising group of bioactive marine natural products. Marine Drugs , 16: 6. DOI: 10.3390/md16010006, 32 p. Garcí  a-Morales, H., L.E. Gutié  r rez-Millá  n, M.A. Valdez, A. Burgos-Herná  ndez, T. Gollas-Galvá  n, and M.G. Burboa, 2016. Antiproliferative activity of protein extracts from the black clam (Chione fluctifraga ) on human cervical and breast cancer cell lines. African Journal of. Biotechnology , 15: 214– 220. Gavagnin, M., A. Fontana, M.L. Ciavatta, and G. Cimino, 2000. Chemical studies on Antarctic nudibranch molluscs. Italian Journal of Zoology , 67 (Supplement 1): 101– 109. Gavagnin, M., N. Ungur, F. Castelluccio, C. Muniain, and G. Cimino, 1999. New minor diterpenoid diacylglycerols from the skin of the nudibranch Anisodoris fontaini . Journal of Natural Products , 62: 269– 274. Ghosh, S., and R.J. Playford, 2003. Bioactive natural compounds for the treatment of gastrointestinal disorders. Clinical Science , 104: 547– 556. Giftson, H., and J. Patterson, 2014. Antibacterial activity of the shell extracts of marine mollusc Donax faba  against pathogens. International Journal of Microbiological Research , 5: 140– 143. Giftson, H., A.E. Mani, I. Jayasanta, S. Kailasam, and J. Patterson, 2015. Antibacterial, biochemical composition and FTIR analysis of Chicoreus ramosus  from Kanyakumari coast. International Journal of Pharmacy and Pharmaceutical Research , 4: 171– 181. Gomes, A.M., E.O. Kozlowskia, V.H. Pominb, C.M. de Barrosa, J.L. Zaganeli, S.G. Mauro, and M.S.G. Pavã oa, 2010. Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus  (Linnaeus, 1758) safely inhibits arterial thrombosis after photo chemically induced endothelial lesion. Journal of Biological Chemistry , 285: 7312– 7323. Gonzá  lez, M.A., 2010. Scalarane sesterterpenoids. Current Bioactive Compounds , 6: 178– 206. Gopeechund, A., R. Bhagooli, V. Sharadha, N. Bhujun, and T. Bahoun, 2015. Antioxidant Activities of Edible Marine Molluscs from a Tropical Indian Ocean Island. Symposium. wiomsa.org/wpcontent/uploads/2015/10/A.-Gopeechund.pdf. Gray, A.P., I.A.N. Lucas, R. Seed, and C.A. Richardson, 1999. Mytilus edulis  chilensis infested with Coccomyxa parasitica  (Chlorococcales, Coccomyxaceae). Journal of Molluscan Studies , 65: 289– 294. Green, T.J., Raftos, D., Speck, P., Montagnani, C., 2015. Antiviral immunity in marine molluscs. Journal of General Virology , 96, 2471– 2482.

179 Gribble, G.W., 2010. Naturally Occurring Organohalogen Compounds— A Comprehensive Update . Springer-Verlag, Wien. Grosso, C., P. Valentã  o, F. Ferreres, and P.B. Andrade, 2014. Bioactive marine drugs and marine biomaterials for brain diseases. Marine Drugs , 12: 2539– 2589. Guenther, J., and R. De Nys, 2006. Differential community development of fouling species on the pearl oysters Pinctada fucata , Pteria penguin  and Pteria chinensis  (Bivalvia, Pteriidae). Biofouling, The Journal of Bioadhesion and Biofilm Research , 22: 151– 159. Gunawarman, A.J., R.I. Gundini, and A. Ahli, 2015. Characterization of bioceramic powder from clamshell (Anadara antiquata ) prepared by mechanical and heat treatments for medical application. Proceeding Seminar Nasional Tahunan Teknik Mesin XIV (SNTTM XIV) , Material 9, 6 p. Gupta, P., M. Arumugam, R.V. Azad, R. Saxena, S. Ghose, N. Ranjan Biswas, T. Velpandian, 2014. Screening of antiangiogenic potential of twenty-two marine invertebrate extracts of phylum Mollusca  from South East Coast of India. Asian Pacific Journal of Tropical Biomedicine , 4: S129– S138. Hamann, M.T., and P.J. Scheuer, 1993. Kahalalide F: A bioactive depsipeptide from the sacoglossan mollusk Elysia rufescens  and the green alga Bryopsis  sp. Journal of the American Chemical Society , 115: 5825– 5826. Hamann, M.T., C.S. Otto, and P.J. Scheuer, 1996. Kahalalides: Bioactive peptides from a marine mollusk Elysia rufescens  and its algal diet Bryopsis  sp. The Journal of Organic Chemistry , 61: 6594– 6600. Han, E.T., and J.Y. Chai, 2008. Mactra veneriformis , an intertidal clam, as a new second intermediate host for Acanthoparyphium marilae  (Digenea: Echinostomatidae). Korean Journal of Parasitology , 46: 101– 104. Han, J.R., J.N. Yan, S.G. Sun, Y. Tang, W.H. Shang, A.T. Li, X.K. Guo, Y.N. Du, H.T. Wu, B.W. Zhu, and Y.L. Xiong, 2018. Characteristic antioxidant activity and comprehensive flavor compound profile of scallop (Chlamys farreri ) mantle hydrolysates-ribose Maillard reaction products. Food Chemistry , 261: 337– 347. Hardjito, L., D.S. Royani, and J. Santoso, 2012. Nutritional composition and topoisomerase inhibitor activity of ethnomedicinal marine mollusk Nerita albicilla . Journal of Food Science and Engineering , 2: 550– 556. Harris, J.R., and J. Markl, 1999. Keyhole limpet hemocyanin (KLH): A biomedical review. Micron , 30: 597– 623. Hasan, T., A.W. Wahab, N. Djide, and M. Zakir, 2015. Antioxidant activity of bioactive protein of kerang kepah (Atactodea striata ) from South Sulawesi. American Journal of Biomedical and Life Sciences , 3: 111– 114. Hasanah, N.F., D. Pringgenies, and S. Wulandari, 2012, Characterization of secondary metabolites bacteria symbion gastropoda Conus miles  with GC-MS methods as antibacterial MDR (Multi Drug Resistant). Journal Of Marine Research , 1: 197– 202. Hashizume, K., N. Tatarazako, K. Kohata, Y. Nakamura, and M. Morita, 2012. Life history characteristics of the surf clam Mactra veneriformis  (Bivalvia: Veneroida: Mactridae) on a sandy tidal flat in Tokyo Bay, Japan. Pacific Science , 66: 335– 346. Hayashi, E., 1975. Pharmacological studies on surugatoxin, the toxic principle from Japanese ivory mollusc (Babylonia japonica ). British Journal of Pharmacology , 53: 207– 215. Himmelman, J.H., and J.-R. Hamel, 1993. Diet, behaviour and reproduction of the whelk Buccinum undatumin  the northern Gulf of St. Lawrence, eastern Canada. Marine Biology , 116: 423– 430.

180 Holmstedt, B., and V.P. Whittaker, 1958. Pharmacological properties of β β -dimethylacryloylcholine and some other β -substituted acryloylcholines. British Journal of Pharmacology , 13: 308– 314. Honari, M., A. Tehranifard, M. Vazirian, A. Salaritabar, H. Sanati, and A.M. Ansari, 2017. Cytotoxic effect of Turbo coronatus extract on cancer cell lines. Research Reviews: Pharmacy & Pharmaceutical Sciences , 6: 55– 58. Hu, X., L. Song, L. Huang, Q. Zheng, and R. Yu, 2012. Antitumor effect of a polypeptide fraction from Arca subcrenata  in vitro and in vivo. Marine Drugs , 10: 2782– 2794. Huang, F., Z. Yang, D. Yu, J. Wang, R. Li, and G. Ding, 2012. Sepia  ink oligopeptide induces apoptosis in prostate cancer cell lines via caspase-3 activation and elevation of Bax/Bcl-2 ratio. Marine Drugs , 10: 2153– 2165. Hubert, F., W. Knaap, T. Noë l, and P. Roch, 1996. Cytotoxic and antibacterial properties of Mytilus galloprovincialis , Ostrea edulis  and Crassostrea gigas  (bivalve molluscs) hemolyrnph. Aquatic Living Resources , 9: 115– 124. Ignatius, B., M. Srinivasan, and S. Balakrishnan, 2011. Reproductive traits of sandbird octopus, Amphioctopus aegina (Gray, 1849) from Mandapam coastal waters (Palk Bay), Southeast Coast of India. Ocean Science Journal , 46: 145. Immanuel, G., B.J. Thaddaeus, M. Usha, R. Ramasubburayan, S. Prakash, and A. Palavesam, 2012. Antipyretic, wound healing and antimicrobial activity of processed shell of the marine mollusc Cypraea moneta . Asian Pacific Journal of Tropical Biomedicine , 2: S1643– S1646. Jagadis, I., K. Shunmugasundaram, Md. Sathakkathulla, and T. Mohanraj, 2013. Spawning, intracapsular development and production potential of viable juveniles of a murex Chicoreus virgineus  var. ponderosa  Sowerby under laboratory conditions. Agricultural Sciences , 4: 244– 248. Jakó  b, M., J. Lubkowski, B.R. O’  Keefe, A. Wlodawer, 2015. Structure of a lectin from the sea mussel Crenomytilus grayanus  (CGL). Acta Crystallographica. Section F, Structural Biology Communications , 71: 1429– 1436. Janaki, M., V. Santhi, and A. Kannagi, 2015. Bioactive potential of Fusinus nicobaricus  from Gulf of Mannar. International Journal of Pharmaceutical Research and Bio-Science , 4: 262– 270. Jayalakshmi, K., P. Ramasamy, V. Shanmugam, and A. Shanmugam, 2017. Isolation and partial characterization of collagen from outer skin of Sepia pharaonis  (Ehrenberg, 1831) from Puducherry coast. Biochemistry and Biophysics Reports , 10: 39– 45. Jayanthi, G., M. Anand, G. Chelladurai, A Kumaraguru, 2016. Bioactive potential of some economically important marine gastropods along the Gulf of Mannar region, southeast coast of India. Journal of Coastal Life Medicine , 4: 608– 611. Je, J.Y., P.J. Park, H.G. Byun, W.K. Jung, and S.K. Kim, 2005. Angiotensin I converting enzyme (ACE) inhibitory peptide derived from the sauce of fermented blue mussel, Mytilus edulis . Bioresource Technology , 96: 1624– 1629. Jensen, K.R. NOBANIS—  Marine invasive species in Nordic waters— Fact Sheet— Mya arenaria  . https​://ww​w.nob​anis.​ org/g​lobal​a sset​s /spe​c iesi​n fo/m​/mya-​a rena​r ia/m​ya-ar​enari​ a.pdf​. Jha, R.K., and X. Zi-rong, 2004. Biomedical compounds from marine organisms. Marine Drugs , 2: 123– 146. Jiang, C., Q. Xiong, D. Gan, Y. Jiao, J. Liu, L. Ma, and X. Zeng, 2013. Antioxidant activity and potential hepatoprotective effect of polysaccharides from Cyclina sinensis . Carbohydrate Polymers , 91: 262– 268.

References Jian-yin, M., G. Xiao-mian, H. Jun-feng, and W. Xian, 2011. New antimicrobial peptides purified directly from Bullacta exarata . African Journal of Pharmacy and Pharmacology , 5: 1508– 1512. Jin, A.H., I. Vetter, S.W. Himaya, P.F. Alewood, R.J. Lewis, and S. Dutertre, 2015. Transcriptome and proteome of Conus planorbis  identify the nicotinic receptors as primary target for the defensive venom. Proteomics , 15: 4030– 4040. Jing-jing, S., L. Hui-Hui, Z. Shi-Quan, W. Xin-Chao, F. Mei-Hua, S. Wang, and L. Zhi, 2014. A novel antimicrobial peptide identified from Mytilus coruscus . Acta Hydrobiologica Sinica , 38: 563– 570. Jordan, R.E., and J.A. Marcum, 1986. Anticoagulantly active heparin from clam (Mercenaria mercenaria ). Archives of Biochemistry and Biophysics , 248: 690– 695. Joy, M., K. Chakraborty, and V. Pananghat, 2016. Comparative bioactive properties of bivalve clams against different disease molecular targets. Journal of Food Biochemistry , 40: 593– 602. Jun, J., E. Chung, K. Lee, and C. Lee, 2014. Gametogenic cycle and size at first sexual maturity in female Chlamys (Azumapecten) farreri farreri  (Jones & Preston, 1904) (Bivalvia: Pectinidae) in western Korea. Invertebrate Reproduction & Development , 58: 235– 244. Jung, W., and S.J. Kim, 2009. Isolation and characterisation of an anticoagulant oligopeptide from blue mussel, Mytilus edulis . Food Chemistry , 117: 687– 692. Jung, W., J. Je, H. Kim, and S. Kim, 2002. A novel anticoagulant protein from Scapharca broughtonii . Journal of Biochemistry and Molecular Biology , 35: 199– 205. Jung, W., N. Rajapakse, and S. Kim, 2005. Antioxidative activity of a low molecular weight peptide derived from the sauce of fermented blue mussel, Mytilus edulis . European Food Research and Technology , 220: 535– 539. Kakou, Y., P. Crews, and G.J. Bakus, 1987. Dendrolasin and latrunculin A from the Fijian sponge Spongia mycofijiensis  and an associated nudibranch Chromodoris lochi . Journal of Natural Products , 50: 482– 484. Kanagasabapathy, S., R. Samuthirapandian, and M. Kumaresan, 2011. Preliminary studies for a new antibiotic from the marine mollusk Melo melo  (Lightfoot, 1786). Asian Pacific Journal of Tropical Medicine , 4: 310– 314. Kanchana, S., R. Vennila, K. Rajesh Kumar, M. Arumugam, and T. Balasubramanian, 2014. Antagonistic and cyto-toxicity activity of mollusc methanol extracts. Journal of Biological Sciences , 14: 60– 66. Karthikeyan, V., A. Gopalakrishnan, R. Vijayakumar, and P. Bharathirajan, 2012. Anticoagulant activity of marine bivalve Donax incarnatus  Lin, 1758 collected from Thazhanguda, southeast coast of India. Asian Pacific Journal of Tropical Biomedicine , 2: S1798– S1801. Katticaran, C.M., 1988. Studies on the biology of the clam Sunetta scripta (linne), from the subtidal waters of Cochin. Ph.D. Thesis, Cochin University of Science and Technology, Cochin. Kaviarasan, T., 2014. Screening of egg capsules of marine gastropod Rapana rapiformis  (Born, 1778) for selected pharmacological properties and biochemical characterization of potential bioactive extracts. Ph.D. Thesis, Pondicherry University. Kawashima, H., and M. Ohnishi, 2006. Occurrence of novel nonmethylene-interrupted C24 polyenoic fatty acids in female gonad lipids of the limpet Cellana grata . Bioscience, Biotechnology, and Biochemistry , 70: 2575– 2578. Kendel, Y., C. Melaun, A. Kurz, A. Nicke, S. Peigneur, J. Tytgat, C. Wunder, D. Mebs, and S. Kauferstein, 2013. Venomous secretions from marine snails of the terebridae family target acetylcholine receptors. Toxins , 5: 1043– 1050.

References Khiri, M.Z.A., K.A. Matori, N. Zainuddin, C.A.C. Abdullah, Z.N. Alassan, N.F. Baharuddin, M.H.M. Zaid, 2016. The usability of ark clam shell (Anadara granosa ) as calcium precursor to produce hydroxyapatite nanoparticle via wet chemical precipitate method in various sintering temperature. SpringerPlus, 5: 1206. Khoo, K.K., Z.P. Feng, B.J. Smith, M.M. Zhang, D. Yoshikami, B.M. Olivera, G. Bulaj, and R.S. Norton, 2009. Structure of the analgesic mu-conotoxin KIIIA and effects on the structure and function of disulfide deletion. Biochemistry , 48: 1210– 1219. Kigoshi, H., K. Kanematsu, and D. Uemura, 1999. Turbotoxins A and B, novel diiodotyramine derivatives from the Japanese gastropod Turbo marmorata . Tetrahedron Letters , 40: 5745– 5748. Kim, S., 2012. Marine medicinal foods: Implications and applications— animals and microbes. Food & Nutrition Research , 65, 523 p. Kim, S., 2013. Marine Nutraceuticals: Prospects and Perspectives . CRC Press, Boca Raton, FL, 464 p. Kim, E., H. Joung, Y. Kim, J. Hwang, C. Ahn, Y. Jeon, S. Moon, B.C. Song, and P. Park, 2012. Purification of a novel anticancer peptide from enzymatic hydrolysate of Mytilus coruscus . Journal of Microbiology and Biotechnology , 22: 1381– 1387. Kim, E., Y. Kim, J. Hwang, and P. Park, 2013. Purification and characterization of a novel anticancer peptide derived from Ruditapes philippinarum . Process Biochemistry , 48: 1086– 1090. Kim, Y., E. Kim, Y. Tang, J. Hwang, S.B. Natarajan, W. Kim, S. Moon, B. Jeon, and P. Park, 2016. Antioxidant and anticancer effects of extracts from fermented Haliotis discus hannai  with Cordyceps militaris  mycelia. Food Science and Biotechnology , 25: 1775– 1782. Kim, Y.H., E. Chung, and Y.G. Kim, 2000. Reproductive ecology and parasite of the venus clam, Cyclina sinensis  (Gmelin), on the West Coast of Korea. The Korean Journal of Malacology , 16: 35– 41. Kim, H., S. Kang, I. Kim, S. Kim, D. Kim, S. Ma, T. Gao, H. Li, M. Kim, T. Lee, and K. Ham, 2006. In vitro anti-hypertensive, antioxidant and anticoagulant activities of extracts from Haliotis discus hannai . Journal of the Korean Society of Food Science and Nutrition , 35: 835– 840. Kim, J.W., B. Lee, J. Kang, and J.S. Lee, 2015. Reproductive cycle of the abalone, Haliotis discus discus  collected from Jeju Island of Korea. The Korean Journal of Malacology , 31: 21– 26. Kim, S., C. Lee, Y. Song, B. Kim, S. Yoon-Hyun, and Y. Lee, 2012. Reproductive cycle of small abalone, Haliotis diversicolor  aquatilis in Jeju Coastal Waters. Development & Reproduction , 16: 145– 153. Kingston, H.M., 2013. Marine bioprospection. 2nd Caribbean ABS Workshop. http:​//www​.abs-​initi​ative​.info​/uplo​ads/m​edia/​2nd­ Ca​r ibbe​anABS​works​hop-3​.4Mey​er.pd​f. Kiran, N., G. Siddiqui, A.N. Khan, K. Ibrar, and P. Tushar, 2014. Extraction and screening of bioactive compounds with antimicrobial properties from selected species of mollusk and crustacean. Journal of Clinical and Cellular Immunology , 5: 189. Konishi, I., M. Hosokawa, T. Sashima, H. Kobayashi, and K. Miyashita, 2006. Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi  induce apoptosis in human leukemia, breast and colon cancer cells. Comparative Biochemistry and Physiology—  Part C: Toxicology & Pharmacology , 142: 53– 59. Koyama, T., R. Chounan, D. Uemura, K. Yamaguchi, and K. Yazawa, 2006. Hepatoprotective effect of a hot-water extract from the edible thorny oyster Spondylus varius  on carbon tetrachloride– induced liver injury in mice. Bioscience, Biotechnology, and Biochemistry , 70: 729– 731.

181 Kudryavtsev, D., T. Makarieva, N. Utkina, E. Santalova, E. Kryukova, C. Methfessel, V. Tsetlin, V. Stonik, and I. Kasheverov, 2014. Marine natural products acting on the acetylcholine-binding protein and nicotinic receptors: From computer modeling to binding studies and electrophysiology. Marine Drugs , 12: 1859– 1875. Kumar, P.A., 2011. Antimicrobial compounds with therapeutic potential from Cerithidea cingulata  against human and fish pathogens. Romanian Biotechnological Letters , 16: 6401– 6406. Kumar, P.S., D.S. Kumar, and S. Umamaheswari, 2015. A perspective on toxicology of Conus venom  peptides. Asian Pacific Journal of Tropical Medicine , 2015: 337– 351. Kurokawa, T.M., M. Wuhrer, G. Lochnit, H. Geyer, J. Markl, and R. Geyer, 2002. Hemocyanin from the keyhole limpet Megathura crenulata  (KLH) carries a novel type of N-glycans with Gal(beta1-6). European Journal of Biochemistry , 269: 5459– 5473. Lango-Reynoso, F., J. Chá  vez-Villaba, and M.L. Pennec, 2006. Reproductive patterns of the Pacific oyster Crassostrea gigas  in France. Invertebrate Reproduction & Development , 49: 41– 50. Lantin-Olaguer, I., and T.U. Bagarinao, 2001. Gonadal maturation, fecundity, spawning and timing of reproduction in the mud snail, Cerithidea cingulata , a pest in milkfish ponds in the Philippines. Invertebrate Reproduction and Development , 39: 195– 207. Lasiak, T., 1986. The reproductive cycle of the intertidal gastropod Turbo coronatus  Gnlelin 1791, on the Transkei coast. African Zoology , 21: 153– 155. Laxmilatha, P., S. Thomas, M.P. Sivadasan, N.P. Ramachandran, and V.G. Surendranathan, 2006. The fishery and biology of Meretrix casta (Chemnitz) in the Moorad estuary, Kerala. Indian Journal of Fisheries, 53: 109–113. Layer, R.T. http:​//www​.jbc.​org/c​onten​t /ear​ly/20​0 0/07​/18/j​bc.M0​ 03619​200.f​ull.p​df. Layer, R.T., and J.M. McIntosh, 2006. Conotoxins: Therapeutic potential and application. Marine Drugs , 4: 119– 142. Lee, J.H., 1999. Gametogenesis and reproductive cycle of the rock shell, Reishia (Thais) clavigera  (Neogastropoda: Muricidae), on the west coast of Korea. Korean Journal of Biological Sciences , 3: 375– 383. Lenin, T., 2011. Biochemical composition and antibacterial activity of marine gastropod Murex virgineus . MSc Thesis, Annamalai University, 30 p. Lenz, T., and G. Boehs, 2011. Reproductive cycle of the mangrove oyster Crassostrea rhizophorae  (Bivalvia: Ostreidae) in Camamu Bay, Bahia, Brasil. Revista de Biologia Tropical , 59: 137– 149. Leonaki, J.L., and K. Lukowiak, 1985. Courtship, copulation, and sperm trading in the sea slug, Navanax inermis  (Opisthobranchia: Cephalaspidea). Canadian Journal of Zoology , 63: 2719– 2729. Li, B., Y. Zhou, S. Guo, and C. Wang, 2007. Polypeptide from Chlamys farreri  inhibits UVB-induced HaCaT cells apoptosis via inhibition CD95 pathway and reactive oxygen species. Free Radical Research , 41: 1224– 1232. Li, C., J. Zhu, Y. Wang, Y. Chen, L. Song, W. Zheng, J. Li, and R. Yu, 2017. Antibacterial activity of AI-hemocidin 2, a novel N-terminal peptide of hemoglobin purified from Arca inflata . Marine Drugs , 15: 205. Li, C.P., N.M. Tauraso, B. Prescott, B.E. Eddy, R.C. Hoye, E.C. Martino, G. Caldes, and C. Gorschboth, 1972. Intratumor therapy in rodents with aqueous clam extracts. Cancer Research , 32: 1201– 1205.

182 Li, G., S. Chen, Y. Wang, Y. Xue, Y. Chang, Z. Li, J. Wang, and C. Xue, 2011. A novel glycosaminoglycan-like polysaccharide from abalone Haliotis discus hannai  Ino: Purification, structure identification and anticoagulant activity. International Journal of Biological Macromolecules , 49: 1160– 1166. Li, L., H. Li, J. Qian, Y. He, J. Zheng, Z. Lu, Z. Xu, and J. Shi, 2016. Structural and immunological activity characterization of a polysaccharide isolated from Meretrix meretrix  Linnaeus. Marine Drugs , 14: 6. Li, Y., F.A. Sadiq, L. Fu, H. Zhu, M. Zhong, and M. Sohail, 2016. Identification of angiotensin I– converting enzyme inhibitory peptides derived from enzymatic hydrolysates of razor clam Sinonovacula constricta . Marine Drugs , 14: 110. Liao, J.H., C.T. Chien, H.Y. Wu, K.F. Huang, I. Wang, M.R. Ho, I.F. Tu, I.M. Lee, W. Li, Y.L. Shih, C.Y. Wu, P.A. Lukyanov, S.T. Hsu, S.H. Wu, 2016. Multivalent marine lectin from Crenomytilus grayanus  possesses anti-cancer activity through recognizing globotriose Gb3. Journal of the American Chemical Society , 138: 4787– 4795. Liao, N., L. Sun, J. Chen, J. Zhong, Y. Zhang, and R. Zhang, 2017. A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells. Molecules, 22: 384. Lin, H., Z. Li, B. Chen, Z. Yi, Z. Wang, and J.M. Hans, 2012. Antitumor activity of the peptide from Bullacta exarata . Journal of Biomedicine , 2: 19– 22. Lipiń ski, M.R., 1987. Food and feeding of Loligo vulgaris reynaudii  from St. Francis Bay, South Africa. South African Journal of Marine Science , 5: 557– 564. Littlejohn, M., 1985. Reproductive patterns of the intertidal limpet, Siphonaria diemenensis  at Griffith Point, Victoria. Australian Ocean Data Network. https​://re​searc​hdata​.ands​.org.​au/re​ produ​ctive​-patt​erns-​inter​tidal​-poin​t-vic​toria​/6799​44. Liu, J.H., 1994. The ecology of the Hong kong limpets Cellana grata (Gould 1859) and Patelloida pygmaea (Dunker 1860): Reproductive biology. Journal of Molluscan Studies , 60: 97– 111. Liu, D., N. Liao, X. Ye, Y. Hu, D. Wu, X. Guo, J. Zhong, J. Wu, and S. Chen, 2013. Isolation and structural characterization of a novel antioxidant mannoglucan from a marine bubble snail, Bullacta exarata  (Philippi). Marine Drugs , 11: 4464– 4477. Liu, H.Z., W. Xiao, Y.P. Gu, Y.X. Tao, D.Y. Zhang, H. Du, and J.H. Shang, 2016. Polysaccharide from Sepia esculenta  ink and cisplatin inhibit synergistically proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells. Iranian Journal of Basic Medical Sciences , 19: 1292– 1298. Liu, L.L. and S.P. Wang, 1999. Population dynamics and mantle autotomy of the figsnail Ficus ficus (Gastropoda: Mesogastropoda: Ficidae). Zoological Studies, 38: 1–6. Liu, R., L. Wang, W. Zheng, and H. Wu, 2015. In vivo antioxidant effects of hydrolysate derived from waste proteins of Mactra veneriformis . Journal of Aquatic Food Product Technology , 24: 143– 152. Liu, R., Y. Zhu, J. Chen, H. Wu, L. Shi, X. Wang, and L. Wang, 2014. Characterization of ACE inhibitory peptides from Mactra veneriformis  hydrolysate by nano-liquid chromatography electrospray ionization mass spectrometry (Nano-LC-ESI-MS) and molecular docking. Marine Drugs , 12: 3917– 3928. Luna-Gonzá  lez, A., A. Maeda-Martí  nez, A. Campa-Có  rdova, a-Rojas, 2007. Antibacterial activity in the and J. Orduñ  hemolymph of the catarina scallop Argopecten ventricosus . Hidrobioló gica , 17: 87– 89. Luo, S., D. Zhangsun, J. Feng, Y. Wu, X. Zhu, and Y. Hu, 2007. Diversity of the O-superfamily conotoxins from Conus miles . Journal of Peptide Science , 13: 44– 53.

References Luppi, E., M. Cesaretti, and N. Volpi, 2005. Purification and characterization of heparin from the Italian clam Callista chione . Biomacromolecules , 6: 1672– 1678. Ma, J., F. Huang, H. Lin, and X. Wang, 2013. Isolation and purification of a peptide from Bullacta exarata  and its impaction of apoptosis on prostate cancer cell. Marine Drugs , 11: 266– 273. Mabrouk, H.B., S. Nejia, M. Maram, M. Naziha, and C.E. Soufia, 2017. A new protein extract inhibitor from hypobranchial purple gland of Hexaplex trunculus , a Mediterranean mollusk, impairs the motility of human glioblastoma U87 and the HeLa cell line of cervical carcinoma cells. Nutrition and Cancer , 69: 1028– 1035. Madhu, V.N., P. Sivaperumal, K. Kamala, A.A. Ambekar, and B.G. Kulkarni, 2014. Antibacterial and antioxidant activities of the tissue extract of Perna viridis Linnaeus, 1758 (Mollusca: Bivalvia) from Versova coast, Mumbai. International Journal of Pharmacy and Pharmaceutical Sciences , 6 (suppl 2): 704– 707. Malhotra, P., P.V.N. Dasaradhi, A. Mohammed, S. Mukherji, V. Manivel, K.V.S. Rao, G.C. Mishra, P.S. Parameswaran, and A. Chatterj, 2003. Use of phosphono derivatives of selected aliphatic acids for anti-malarial activity. Indian Patent # 0268NF. Maoka, T., and T. Matsuno, 1988. Isolation and structural elucidation of three new acetylenic carotenoids from the Japanese sea mussel Mytilus coruscus . Bulletin of the Japanese Society of Scientific Fisheries (Nippon Suisan Gakkaishi) , 54: 1443– 1447. Maramorosch, K., 2012. Invertebrate Immunity . Elsevier, Cambridge, 378 p. Mariappan, R., V. Sukumaran, and M. Ayyavoo, 2010. Potential antibacterial activity of marine bivalves Meretrix casta  and Tridacna maxima  from South East Coast of India. Advances in Bioresearch , 1: 92– 96. Marsault, E., and M.L. Peterson, 2017. Practical Medicinal Chemistry with Macrocycles: Design, Synthesis, and Case Studies . John Wiley & Sons, Inc. Martí nez-Castro, C., and E. Vá zquez, 2012. Reproductive cycle of the cockle Cerastoderma edule  (Linnaeus 1758) in the Rí a De Vigo (Galicia, Northwest Spain). Journal of Shellfish Research , 31: 757– 767. Mayer, A.M.S., and R.K. Gustafson, 2003. Marine pharmacology in 2000: Antitumor and cytotoxic compounds. International Journal of Cancer , 105: 291– 299. Mayer, A.M.S., and K.R. Gustafson, 2006. Marine pharmacology in 2003– 2004: Anti-tumour and cytotoxic compounds. European Journal of Cancer , 42: 2241– 2270. Mayer, A.M.S., and M.T. Hamann, 2002. Marine pharmacology in 1999: Compounds with antibacterial, anticoagulant, antifungal, anthelmintic, anti-inflammatory, antiplatelet, antiprotozoal and antiviral activities affecting the cardiovascular, endocrine, immune and nervous systems, and other miscellaneous mechanisms of action. Comparative Biochemistry and Physiology— Part C , 132: 315– 339. Mayer, A.M.S., K.B. Glaser, C. Cuevas, C.R.S. Jacobs, W. Kem, R.D. Little, J.M. McIntosh, D.J. Newman, B.C. Potts, and D.E. Shuster, 2010. The odyssey of marine pharmaceuticals: A current pipeline perspective. Trends in Pharmacological Sciences , 31: 255– 265. McFadden, D.W., D.R. Riggs, B.J. Jackson, and L. Vona-Davis, 2003. Keyhole limpet hemocyanin, a novel immune stimulant with promising anticancer activity in Barrett’ s esophageal adenocarcinoma. American Journal of Surgery , 186: 552– 555. Mercado, L., P. Schmitt, S.H. Marshall, and G. Arenas, 2005. Gill tissues of the mussel Mytilus edulis chilensis : A new source for antimicrobial peptides. Electronic Journal of Biotechnology , 8: 284-290.

References Merdekawati, D., 2013. Nutrition content and antioxidant compound of the rough turban snails (Turbo setosus Gmelin 1791). http:​// rep​osito​r y.ip​b.ac.​id/bi​tstre​a m/ha​ndle/​12345​6789/​66859​/2013​ dme.p​df?se​quenc​e=1&i​sAllo​wed=y​. Milione, M. and P. Southgate, 2011. Seasonal Changes in Recruitment of Pteria penguin in North Queensland, Australia. Journal of Shellfish Research, 30: 89–94. Mirshahi, M., P. Mirshahi, S. Negro, J. Soria, P.K. Sreekumar, S. Kotnala, A. Therwath, and A.C.J. Pertanika, 2009. Extract of Indian green mussel, Perna viridis  (L.) shows inhibition of blood capillary formation in vitro. Tropical Agricultural Science , 32: 35– 42. Mitta, G., F. Hubert, T. Noë l, and P. Roch, 1999. Myticin, a novel cysteine‐  r ich antimicrobial peptide isolated from haemocytes and plasma of the mussel Mytilus galloprovincialis . The FEBS Journal , 265: 71– 78. Miyamoto, T., K. Sakamoto, K. Arao, T. Komori, and T. Sasaki, 1996. Dorisenones, cytotoxic spongian diterpenoids, from the nudibranch Chromodoris obsoleta . Tetrahedron , 52: 8187– 8198. Mohan, K., P. Abirami, S. Kanchana, and M. Arumugam, 2016. Isolation and characterization of Molluscan glycosaminoglycans from Pazhayar, South-East coast of India. International Journal of Fisheries and Aquatic Studies , 4, 100– 105. Mohanraj, T., K. Prabhu, and S. Lakshmanasenthil, 2012. Antimicrobial activity of Pteria penguin  against human pathogens from the Southeast Coast of India. International Journal of Pharmacy and Biological Sciences , 3: 65– 70. Mohanraju, R., D.B. Marri, P. Karthick, S. Narayana, K.N. Murthy, and Ch. Ramesh, 2013. Antibacterial activity of certain cephalopods from Andamans, India. International Journal of Pharmacy and Biological Sciences , 3: 450– 455. Moltedo, B., F. Faunes, D. Haussmann, P. De Ioannes, and A.E. De Ioannes, 2006. Immunotherapeutic effect of Concholepas hemocyanin in the murine bladder cancer model: Evidence for conserved antitumor properties among hemocyanins. Journal of Urology , 176: 2690– 2695. Moncheva, S., J. Namiesnik, R. Apak, P. Arancibia-Avila, F. Toledo, S. Kang, S. Jung, and S. Gorinstein, 2011. Rapana venosa  as a bioindicator of environmental pollution. Chemistry and Ecology , 27: 31– 41. Monolisha, S., A.E. Mani, J. Patterson, and J.K.P. Edward, 2013. Molecular characterization and antimicrobial activity of Octopus aegina  and Octopus dolfusii  in Gulf of Mannar coast. International Journal of Pharmaceutical Sciences and Research , 4: 3582– 3587. Moreno-Fé  lix, C., G. Wilson-Sá  nchez, S. Cruz-Ramí  rez, C. Velá  zquez-Contreras, M. Plascencia-Jatomea, A. Acosta, L. Machi-Lara, M. Aldana-Madrid, J. Ezquerra-Brauer, F. Rocha-Alonzo, and A. Burgos-Herná ndez, 2013. Bioactive lipidic extracts from octopus (Paraoctopus limaculatus ): Antimutagenicity and antiproliferative studies. EvidenceBased Complementary and Alternative Medicine , 2013: 273582, 12 p. Morton, B., 1980. Swimming in Amusium pleuronectes (Bivavia: Pectinidae). Journal of Zoology , 190: 375– 404. Mudianta, W., N.W. Martiningsih, I.N.D. Prasetia, and M. Nursid, 2016. Bioactive terpenoid from the balinese nudibranch Hypselodoris infucata . Indonesian Journal of Pharmacy , 27: 104– 110. Murphy, K.J., N.J. Mann, and A.J. Sinclair, 2002. Fatty acid and sterol composition of frozen and freeze-dried New Zealand green lipped mussel (Perna canaliculus ) from three sites in New Zealand. Proceedings of the Nutrition Society of Australia , 26: S305.

183 Muthu, T.P., and D. Selvaraj, 2015. Analysis of bioactive constituents from the flesh of Turbo brunneus  (Roding, 1798) by GCMS. International Journal of Fisheries and Aquatic Studies , 3: 257– 259. Nadarajah, S., R. Vijayaraj, and J. Mani, 2017. Therapeutic significance of Loligo vulgaris  (Lamarck, 1798) ink extract: A biomedical approach. Pharmacognosy Research , 9: S105– S109. Nair, D.G., R. Weiskirchen, and S.K. Al-Musharafi, 2015. The use of marine-derived bioactive compounds as potential hepatoprotective agents. Acta Pharmacologica Sinica , 36: 158– 170. Nair, K.V. and K.S. Rao, 1974. The commercial molluscs of India. CMFRI Bull., 5: 168. Navarro, J.M., and J. Widdows, 1997. Feeding physiology of Cerastoderma edule  in response to a wide range of seston concentrations. Marine Ecology Progress Series , 152: 175– 186. Nayak, S.K., 2011. Biopharmaceutical potential of the venom of selected coniids from Indian waters. Ph.D. Thesis, Central Institute of Fisheries Education, Mumbai, India. Nazeer, R.A., K.R. Prabha, N.S. Kumar, and R.J. Ganesh, 2013. Isolation of antioxidant peptides from clam, Meretrix casta  (Chemnitz). Journal of Food Science and Technology , 50: 777– 783. Nazeer, R.A., M.A.V. Saranya, and S.Y. Naqash, 2014. Radical scavenging and amino acid profiling of wedge clam, Donax cuneatus  (Linnaeus) protein hydrolysates. Journal of Food Science and Technology , 51: 3942– 3948. Nigmatullin, C., K. Nesis, and A. Arkhipkin, 2001. A review of the biology of the jumbo squid Dosidicus gigas  (Cephalopoda: Ommastrephidae). Fisheries Research , 54: 9– 19. Ninan, L., R.L. Stroshine, J.J. Wilker, and R. Shi, 2007. Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa. Acta Biomaterialia , 3: 687– 694. Ning, X., J. Zhao, Y. Zhang, S. Cao, M. Liu, P. Ling, and X. Lin, 2009. A novel anti-tumor protein extracted from Meretrix meretrix  Linnaeus induces cell death by increasing cell permeability and inhibiting tubulin polymerization. International Journal of Oncology , 35: 805– 812. Noble, W.J., 2014. Aspects of life history and ecology of Dicathais orbita  (Gmelin, 1781) related to potential aquaculture for bioactive compound recovery. Ph.D. Thesis, Flinders University. Nongmaithem, B.V., P. Mouatt, J. Smith, D. Rudd, M. Russell, C. Sullivan, and K. Benkendorf, 2017. Volatile and bioactive compounds in opercula from Muricidae molluscs supports their use in ceremonial incense and traditional medicines. Scientific Reports , 7: 17404, 14 p. Novoa, B., A. Romero, Á .L. Á lvarez, R. Moreira, P. Pereiro, M.M. Costa, S. Diosa, A. Estepa, F. Parra, and A. Figueras, 2016. Antiviral activity of myticin C peptide from mussel: An ancient defence against herpes viruses. Journal of Virology , 90: 7692– 7702. Ochi, M., K. Kataoka, S. Ariki, C. Iwatsuki, M. Kodama, and Y. Fukuyama, 1998. Antioxidative bromoindole derivatives from the mid-intestinal gland of the muricid gastropod Drupella fragum . Journal of Natural Products , 61: 1043– 1045. O’  Connor, W.A., and N.F. Lawler, 2004. Reproductive condition of the pearl oyster, Pinctada imbricata , Rö ding, in Port Stephens, New South Wales, Australia. Aquaculture Research , 35: 385– 396. Ohnoki, S., Y. Mitomi, R. Hata, and K. Satake, 1973. Heterogeneity of hemoglobin from arca (Anadara satowi ) molecular weights and oxygen equilibria of arca Hb I and II. The Journal of Biochemistry , 73: 717– 725.

184 Oliaei, S., E. Etemadi-Deylami, B. Heidari, and Z. Farahnejad, 2015. Antifungal activity of organic and aqueous extractions in Plakobranchus ocellatus  (Gastropoda: Sacoglossa) against Candida albicans , C. parapsilosis  and C. glabrata . Microbiology Journal , 5: 1– 8. Oliviera, A.P., A. Lobo-da-Cunha, M. Taveira, M. Ferreira, P. Valentã  o, and P.B. Andrade, 2015. Digestive gland from Aplysia depilans  Gmelin: Leads for inflammation treatment. Molecules , 20: 15766– 15780. Onitsuka, T., T. Kawamura, T. Horii, N. Takiguchi, H. Takami, and Y. Watanabe, 2007. Synchronized spawning of abalone Haliotis diversicolor triggered by typhoon events in Sagami Bay, Japan. Marine Ecology Progress Series, 351: 129–138. Orekhov, A.N., 2013. Anti-atherosclerotic drugs from natural products. Natural Products Chemistry and Research , 1: 121. DOI: 10.4172/2329-6836.1000121. Orlando, P., F. Carretta, P. Grippo, G. Cimino, S. De Stefano, and G. Strazzullo, 1991. Kelletinin I and kelletinin A from the marine mollusc Buccinulum corneum  are inhibitors of eukaryotic DNA polymerase. Experientia , 47: 64– 66. Ovodova, R.G., V.E. Glazkova, L.V. Mikheyskaya, V.I. Molchanova, V.V. Isakov, Y.S. Ovodov, and L.E.F. Molina, 1992. The structure of mytilan, a bioglycan-immunomodulator isolated from the mussel Crenomytilus grayanus . Carbohydrate Research , 223: 221– 226. Pachaiyappan, A., A. Muthuvel, G. Sadhasivam, V.J.V. Sankar, N. Sridhar, and M. Kumar, 2014a. In vitro antioxidant activity of different gastropods, bivalves and echinoderm by solvent extraction method. International Journal of Pharmaceutical Sciences and Research, 58: 2539– 2545. Pachaiyappan, A., G. Sadhasivam, M. Kumar, and A. Muthuvel, 2014b. Antibacterial activity of different solvent extracts of marine bivalve, Meretrix casta . Current Biotica , 8: 270– 277. Pakrashi, A., P. Roy, and V. Datta, 2001. Antimicrobial effect of protein(s) isolated from a marine mollusc Telescopium telescopium . Indian Journal of Physiology and Pharmacology , 45: 249– 252. Pan, B.P., Q. Wu, S.P. Zhang, L.S. Song, and W.J. Bu, 2006. Molecular phylogeny of Meretrix (Mollusca, Bivalvia) based on 16S rRNA and ITS1 sequences [J]. Oceanologia Etlmnologia Snica, 37: 342–347. Pandian, V., and S. Thirugnanasambandan, 2008. Glycosamino­ glycans (GAG) from backwater clam Marcia opima . Iranian Journal of Pharmacology and Therapeutics , 7: 147– 151. Pangestuti, R., and S. Kim, 2017. Bioactive peptide of marine origin for the prevention and treatment of non-communicable diseases. Marine Drugs , 15: 1– 23. Park, M.W., H. Kim, B.H. Kim, H. Byeong, M.H. Son, J.S. Choi, and J.S. Lee, 2014. Reproductive cycle of the abalone, Haliotis discus hannai  collected from Jindo of Korea. The Korean Journal of Malacology , 30: 243– 248. Parrish, S.M., W. Yoshida, B. Yang, and P.G. Williams, 2017. Ulapualides C– E Isolated from a Hawaiian Hexabranchus sanguineus  egg mass. Journal of Natural Products , 80: 726– 730. Pati, P., B.K. Sahu, and R.C. Panigrahy, 2015. Marine molluscs as a potential drug cabinet: An overview. Indian Journal of GeoMarine Sciences , 44: 961– 970. Pavã o, M.S.G., and P.A.S. Mourã o, 2012. Challenges for heparin production: Artificial synthesis or alternative natural sources? Glycobiology Insights , 3: 1– 6. Pawar, R.T., S.S. Nagvenkar, T.G. Jagtap, and T.B. Dergisi, 2013. Protective role of edible clam Paphia malabarica  (Chemnitz) against lipid peroxidation and free radicals. Turkish Journal of Biochemistry , 38: 138– 144.

References Pejler, G., A. Danielsson, I. Bjork, U. Lindahl, H.B. Nader, and C.P. Dietrich, 1987. Structure and antithrombin-binding properties of heparin isolated from the clams Anomalocardia brasiliana  and Tivela mactroides . Journal of Biological Chemistry , 262: 11413– 11421. Pereira, R.B., P.B. Andrade, and P. Valentã o, 2016. Chemical diversity and biological properties of secondary metabolites from sea hares of Aplysia  genus. Marine Drugs , 14: 39. Periyasamy, N., S. Arularasan, and S. Gayathri, 2012. Antibacterial activity of the tissue extracts of Conus betulinus  and Conus inscriptus  Linnaeus, 1758 (Mollusca: Gastropoda) from Nagapattinam, Southeast coast of India. Asian Pacific Journal of Tropical Disease , 2: S914– S919. Periyasamy, N., S. Murugan, and P. Bharadhirajan, 2013a. Anticoagulant activity of marine gastropods Babylonia spirata  (Lin, 1758) and Phalium glaucum  (Lin, 1758) collected from Cuddalore, southeast cost of India. International Journal of Pharmacy and Pharmaceutical Sciences , 5: 117– 121. Periyasamy, N., S. Murugan, and P. Bharadhirajan, 2013b. Isolation and characterization of anticoagulant compound from marine mollusc Donax faba  (Gmelin, 1791) from Thazhanguda, Southeast Coast of India. African Journal of Biotechnology , 12: 5968– 5974. Periyasamy, N., M. Srinivasan, and S. Balakrishnan, 2012. Antimicrobial activities of the tissue extracts of Babylonia spirata  (Linnaeus, 1758) (Mollusca: Gastropoda) from Thazhanguda, southeast coast of India. Asian Pacific Journal of Tropical Biomedicine , 2: 36– 40. Petsut, N., and S. Kulabtong, 2013. Biology of Indian squid, Loligo duvauceli  in Thailand. Veridian E-Journal , 6: 1004– 1009. Pettit, G.R., Y. Tang, and J.C. Knight, 2005. Antineoplastic agents 545. Isolation and structure of turbostatins 1– 4 from the Asian marine mollusc Turbo stenogyrus . Journal of Natural Products , 68: 974– 978. Piyathamrongrut, K., K. Kanjanachatree, L. Thongboon, and J. Inthoncharoen. Reproductive cycle of the akoya pearl oyster (Pinctada fucata ) belong to nucleus insertion. http:​//www​.lib.​ ku.ac​.th/K​UCONF​/data​52/KC​47040​34.pd​f. Ponder, W.F., and J. Cooper, 1983. A revision of the recent xenophoridae of the world and of the Australian fossil species (Mollusca: Gastropoda). The Australian Museum, Sydney, Memoir 17. Ponnusamy, K., K. Kamala, S. Munilkumar, and A.K. Pal, 2016. Antioxidant properties from tissue extract of cephalopods around Madras Atomic Power Station, Kalpakkam Coast. International Journal of Pharma Research and Health Sciences , 4: 1086– 1091. Pringgenies, D., 2010. Characteristic bioactive compound of the mollusc symbiotic bacteria by using GC-MC. Journal of Tropical Marine Science and Technology , 2: 34– 40. Purwaningsih, S., 2012. Aktivitas antioksidan dan komposisi kimia keong matah merah (Cerithidea obtusa ). Ilmu Kelautan Maret , 17: 39– 48. Qian, Z., Z. FuLai, W. Ling, Z. LingJing, and C.M. Jie, 2014. Extraction and determination of taurine from viscera of abalone (Haliotis discus hannai ). Journal of Food Safety and Quality , 5: 70– 76. Qian, Z., W. Jung, H.G. Byun, and S. Kim, 2008. Protective effect of an antioxidative peptide purified from gastrointestinal digests of oyster, Crassostrea gigas  against free radical induced DNA damage. Bioresource Technology , 99: 3365– 3371. Qian-qun, G., F. Yu-chun, W. Chang-yun, X. Hang, and Q. Yu-qing, 1998. Studies on the antitumor activity and isolation of the glycoprotein from the gonad of Chlamys (Azumapecten) farreri . Chinese Journal of Oceanology and Limnology , 16: 359– 363.

References Qiao, M., M. Tu, Z. Wang, F. Mao, H. Chen, L. Qin, and M. Du, 2018. Identification and antithrombotic activity of peptides from blue mussel (Mytilus edulis ) protein. International Journal of Molecular Sciences , 19: 138. DOI: 10.3390/ijms19010138, 12 p. Qing, L., 2009. Studies on the reproductive biology of Neverita didyma . Master’ s Thesis, Lu Tung University. Qu, Y., Y. Xu, B. Wang, and X. Wang, 2011. Preparation and antioxidant properties of the hydrolysate and frations from Mytilus edulis  by papain. 2011 International Conference on Remote Sensing, Environment and Transportation Engineering, RSETE 2011 - Proceedings. 10.1109/RSETE.2011.5964116. Raj, J.M., G. Chelladurai, P., Ramasamy, and P.K. Deepa, 2014. Antibacterial attributes of marine gastropod Hemifusus pugilinus  (Born, 1778) against human pathogenic bacteria. International Journal of Marine Science , 4: 1– 4. Raja, R., A. Sabapathi, and V. Sankar, 2017. Antibiotic activity of different solvent extracts of the marine gastropod Thais bufo  against Staphylococcus aureus  and Streptococcus pyogenes . Journal of Coastal Life Medicine , 5: 7– 12. Rajaganapathi, J., K. Rajagopal, and J.K.P. Edward, 2001. Antifungal and cytotoxic effects of methanol extracts of three marine molluscs. Indian Journal of Experimental Biology , 39: 85– 86. Ramasamy, M., and U. Balasubramanian, 2012. Identification of bioactive compounds and antimicrobial activity of marine clam Anadara granosa  (Linn.). International Journal of Science and Nature , 3: 263– 266. Ramasamy, P., and A. Shanmugam, 2015. Characterization and wound healing property of collagen-chitosan film from Sepia kobiensis  (Hoyle, 1885). International Journal of Biological Macromolecules , 74: 93– 102. Ramasamy, P., N. Subhapradha, V. Shanmugam, and A. Shanmugam, 2014a. Extraction, characterization and antioxidant property of chitosan from cuttlebone Sepia kobiensis  (Hoyle 1885). International Journal of Biological Macromolecules , 64: 202– 212. Ramasamy, P., N. Subhapradha, V. Shanmugam, and A. Shanmugam, 2014b. Protective effect of chitosan from Sepia kobiensis  (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury. International Journal of Biological Macromolecules , 65: 559– 563. Ramasamy, P., N. Subhapradha, A. Srinivasan, V. Shanmugam, J. Krishnamoorthy, and A. Shanmugam, 2011. In vitro evaluation of antimicrobial activity of methanolic extract from selected species of Cephalopods on clinical isolates. African Journal of Microbiology Research , 5: 3884– 3889. Ramesh, S., V. Sankar, and R. Santhanam, 2012. Marine Pharmaceutical Compounds . Lambert Academic Publishing, 249 p. Ramya, M.S., S. Ravichandran, and R. Anbuchezhian, 2014. In vitro antioxidant properties of marine sea slug Armina babai  from Pazhayaar, Southeast coast of India. International Journal of Natural Products Research , 4: 105– 109. Ramya, M.S., K. Sivasubramanian, S. Ravichandran, and R. Anbuchezhian, 2014. Screening of antimicrobial compound from the sea slug Armina babai . Bangladesh Journal of Pharmacology , 9: 268– 274. Rao, M.B., 1973. Sex phenomenon and reproductive cycle in the limpet Cellana radiata  (Born) (Gastropoda: Prosobranchia). Journal of Experimental Marine Biology and Ecology , 12: 263– 278. Rao, K.V., M. Na, J.C. Cook, J. Peng, R. Matsumoto, and M.T. Hamann, 2008. Kahalalides V– Y Isolated from a Hawaiian collection of the Sacoglossan Mollusk Elysia rufescens . Journal of Natural Products , 71: 772– 778.

185 Rao, K.V.S., M.R. Wani, V. Manivel, P.S. Parameswaran, V.K. Singh, R.V. Anand, E. Desa, G.C. Mishra, and A. Chatterji, 2003. Novel molecules to develop drug for the treatment of osteoporosis. Indian Patent #0412NF2003, US, 30/12/2003, 10/747, 671. Ravi, C., A. Karthiga, and V. Venkatesan, 2012. Isolation and biomedical screening of the tissue extracts of two marine gastropods Hemifusus pugilinus  (Born, 1778) and Natica didyma  (Roding, 1798). Asian Fisheries Science , 25: 158– 169. Ravichandiran, M., S. Thiripurasalini, V. Ravitchandirane, S. Gopalane, C. Stella, 2013. Chemical constituents and antituberculosis activity of ink extracts of cuttlefish, Sepiella inermis . Journal of Coastal Life Medicine , 1: 273– 277. Reddy, K.V., R. Mohanraju, K.N. Murthy, C. Ramesh, and P. Karthick, 2015. Antimicrobial properties of nudibranchs tissues extracts from South Andaman, India. Journal of Coastal Life Medicine , 3: 582– 584. Ren, Y., H. Zhang, B. Pan, C. Yan, 2015. A Kazal-type serine proteinase inhibitor from Cyclina sinensis  is involved in immune response and signal pathway initiation. Fish & Shellfish Immunology , 47: 110– 116. Renaud, M.L., 1976. Observations on the behavior and shell types of Cypraea moneta  (Mollusca, Gastropoda) at Enewetak, Marshall Islands. Pacific Science , 30: 147– 158. Rho, H., H. Kim, J. Kim, F. Karadeniz, B. Ahn, K. Nam, Y. Seo, and C. Kong, 2015. Anti-inflammatory effect of by-products from Haliotis discus hannai  in RAW 264.7 cells. Journal of Chemistry , 2015, 7 p. Ribeiro, P.A., R. Xavier, A.M. Santos, and S.J. Hawkins, 2009. Reproductive cycles of four species of Patella  (Mollusca: Gastropoda) on the northern and central Portuguese coast. Journal of the Marine Biological Association of the United Kingdom , 89: 1215– 1221. Roch, P., Y. Yang, M. Toubian, and A. Aumelas, 2008. NMR structure of mussel mytilin, and antiviral– antibacterial activities of derived synthetic peptides. Developmental & Comparative Immunology , 32: 227– 238. Rodriguez, J., R. Riguera, and C. Debitus, 1991. Cytotoxic bispyrones from Onchidium sp.: Absolute stereochemistry of onchitriols 1 and II. Troisiè me Symposium sur les substances naturelles d’ inté rê t biologique de la ré gion Pacifique-Asie , Noumé a, Nouvelle Calé donie, p. 86. Rohini, B., C.S. Priya, A. Lavanya, K. Kalpana, and V. Karthika, 2012. Potential of water and methanol extracts of Lambis lambis  against fish and human pathogens. Biological Rhythm Research , 43: 205– 213. Romanenkoa, L.A., M. Uchinob, N.I. Kalinovskayaa, and V.V. Mikhailova, 2008. Isolation, phylogenetic analysis and screening of marine mollusc-associated bacteria for antimicrobial, hemolytic and surface activities. Microbiological Research , 163: 633– 644. Romeo, C., L., Di Francesco, M. Oliverio, P. Palazzo, G.R. Massilia, P. Ascenzi, F. Polticelli, and M.E. Schininà , 2008. Conus ventricosus venom peptides profiling by HPLC-MS: A new insight in the intraspecific variation. Journal of Separation Science , 31: 488– 498. Roussis, V., J.R. Pawlik, M.E. Hay, and W. Fenical, 1990. Secondary metabolites of the chemically rich ascoglossan, Cyerce nigricans . Experimentia , 46: 327– 329. Roy, S., U. Datta, D. Ghosh, P.S. Dasgupta, P. Mukherjee, and U. Roychowdhury, 2010. Potential future applications of spermatheca extract from the marine snail Telescopium telescopium . Turkish Journal of Veterinary and Animal Sciences , 34: 533– 540. Ró ż ań ska, H., M. Michalski, and J. Osek, 2012. Antibacterial activity of tissues of bivalve molluscs available on Polish market. Bulletin of theVeterinary InstituteinPulawy , 56: 569– 571.

186 Ruiz-Torres, V., J.A. Encinar, M. Herranz-Ló pez, A. Pé rez-Sá nchez, V. Galiano, E. Barrajó n-Catalá n, and Vi. Micol, 2017. An updated review on marine anticancer compounds: The use of virtual screening for the discovery of small-molecule cancer drugs. Molecules , 22: 1037. DOI: 10.3390/molecules22071037. Rungprom, W., W. Chavasiri, U. Kokpol, A. Kotze, and M.J. Garson, 2004. Bioactive chromodorolide diterpenes from an aplysillid sponge. Marine Drugs , 2: 101– 107. Sadhasivam, G., A. Muthuvel, R. Rajasekaran, A. Pachaiyappan, and B. Thangavel, 2014. Studies on biochemical and biomedical properties of Conus betulinus  venom. Asian Pacific Journal of Tropical Disease , 4: S102– S110. Samanta, S.K., D. Adhikari, S. Karmakar, A. Dutta, A. Roy, K.T. Manisenthil, D. Roy, J.R. Vedasiromoni, and T. Sen, 2008. Pharmacological and biochemical studies on Telescopium Telescopium — a marine mollusk from the Mangrove regions. Oriental Pharmacy and Experimental Medicine , 8: 386– 394. Sá  nchez, A.M., S. Malagarie-Cazenave, N. Olea, D. Vara, C. Cuevas, I. Dí az-Laviada, 2008. Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCzeta activation. European Journal of Pharmacology , 584: 237– 245. Sanduja, R., S.K. Sanduja, A.J. Weinheimer, M. Alam, and G.E. Martin, 1986. Isolation of the cembranolide diterpenes dihydrosinularin and 11-epi-sinulariolide from the marine mollusk Planaxis sulcatus . Journal of Natural Products , 49: 718– 719. Santhanam, R., 2018. Biology and Ecology of Edible Marine Gastropod Molluscs, Apple Academic Press, New Jersey, 460. Santhanam, R., 2018. Biology and Ecology of Edible Marine Gastropod Molluscs, vol. 2, Apple Academic Press, New Jersey, 176. Santhi V., V. Sivakumar, S. Jayalakshmi, R.D. Thilaga, and M., Mukilarasi, 2016. Isolating bioactive compound from marine prosobranch Purpura persica  from Tuticorin Coast. International Journal of Environmental Protection and Policy , 4: 64– 76. Santhi, V., V. Sivakumar, A. Thangathirupathi, and R.D. Thilaga, 2011. Analgesic, anti-pyretic and anti-inflammatory activities of chloroform extract of prosobranch mollusc Purpura persica . International Journal of Pharmacology & Biological Sciences , 5: 9– 15. Sarizan, N.M.B., 2013. Identification of anti-atherosclerotic compounds from marine molluscs of Bidong Archipelago. M.Sc. Thesis of Universiti Malaysi, Teregganu. Sasaki, J., M. Wang, J. Liu, J. Wang, H. Uchisawa, and C. Lu, 2011. Fired shell powder of bivalve Corbicula japonica improves malfunction of liver— Possible development of multi-functional calcium. Journal of US– China Medical Science , 8: 449– 457. Sathyan, N., E.R. Chaithanya, P.R.A. Kumar, K.S. Sruthy, R. Philip, 2014. Comparison of the antimicrobial potential of the crude peptides from various groups of marine molluscs. International Journal of Research in Marine Sciences , 3: 16– 22. Sathyan, N., R. Philip, E.R. Chaithanya, and P.R. Anil Kumar, 2012. Identification and molecular characterization of molluscin, a histone-H2A-derived antimicrobial peptide from molluscs. ISRN Molecular Biology , 219656, 6 p. Schmeer, M.R., and G. Beery, 1965. Mercenone growth inhibitor extracted from the clam, Mercenaria campechiensis . A preliminary investigation of in vivo and in vitro activity. Life Sciences , 4: 2157– 2163. Schwartsmann, G., A.B. Rocha, R.G.S. Berlinck, and J. Jimeno, 2001. Marine organisms as a source of new anticancer agents. The Lancet Oncology , 2: 221– 225.

References Scotti, P.D., S.C. Dearing, D.R. Greenwood, and R.D. Newcomb, 2001. Pernin: A novel, self-aggregating haemolymph protein from the New Zealand greenlipped mussel, Perna canaliculus  (Bivalvia: Mytilidae). Comparative Biochemistry and Physiology, Part-B , 128: 767– 779. See, G.L.L., Y.C. Deliman, J.F.V. Arce, and A. Ilano, 2016. Cytotoxic and genotoxic studies on the mucus of Indian volute Melo broderipii  (Gmelin 1758) and spider conch Lambis lambis  (Linn. 1758). Journal of Pharmacognosy and Natural Products , 2: 120. Seeli, J., 2004. A study of some aspects of biology of scallops in Gulf of Mannar, southeast coast of India. Ph.D. Thesis, Manonmaniam Sundaranar University. Seraspe, E.B., and M. Abaracoso, 2014. Screening of extracts of diwal (Pholas orientalis ) for antimicrobial activities. Journal of Aquaculture & Marine Biology , 1: 00002. Shanmugam, A., K. Kathiresan, and L. Nayak, 2016. Preparation, characterization and antibacterial activity of chitosan and phosphorylated chitosan from cuttlebone of Sepia kobiensis  (Hoyle, 1885). Biotechnology Reports , 9: 25– 30. Shanmugam, V., P. Ramasamy, N. Subhapradha, S. Sudharsan, P. Seedevi, M. Moovendhan, J. Krishnamoorthy, A. Shanmugam, and A. Srinivasan, 2012. Extraction, structural and physical characterization of type I collagen from the outer skin of Sepiella inermis  (Orbigny, 1848). African Journal of Biotechnology , 11: 14326– 14337. Shenai-Tirodkar, P.S., M. Gauns, M.W.A. Mujawar, Z.A. Ansari, 2017. Antioxidant responses in gills and digestive gland of oyster Crassostrea madrasensis  (Preston) under lead exposure. Ecotoxicology and Environmental Safety , 142: 87– 94. Shon, K.J., A. Hasson, M.E. Spira, l.J. Cruz, W.R. Gray, and B.M. Olivera, 1994. Delta-conotoxin GmVIA, a novel peptide from the venom of Conus gloriamaris . Biochemistry , 33: 11420– 11425. Š ifner, S.K., and N. Vrgoč , 2004. Population structure, maturation and reproduction of the European squid, Loligo vulgaris , in the Central Adriatic Sea. Fisheries Research , 69: 239– 249. Silas, E.G., K.S. Rao, R. Sarvesan, K.P. Nair, and M.M. Meiyappan, 1984. The exploited squid and cuttlefish resources of India: A review. CMFRI, Technical and Extension Series , No. 34. Silvestri, I., L. Albonici, M. Ciotti, M.P. Lombardi, P. Sinibaldi, V. Manzari, P. Orlando, F. Carretta, G. Strazzullo, and P. Grippo, 1995. Antimitotic and antiviral activities of kelletinin A in HTLV-1 infected MT2 cells. Experientia , 51: 1076-1080. Somerville, M.J., P.L. Katavic, L.K. Lambert, G.K. Pierens, J.T. Blanchfield, G. Cimino, E. Mollo, M. Gavagnin, M.G. Banwell, and M.J. Garson, 2012. Isolation of thuridillins D– F, diterpene metabolites from the Australian sacoglossan mollusk Thuridilla splendens ; relative configuration of the epoxylactone ring. Journal of Natural Products , 75: 1618– 1624. Soon, T.K., J. Ransangan, 2014. A review of feeding behavior, growth, reproduction and aquaculture site selection for greenlipped mussel, Perna viridis . Advances in Bioscience and Biotechnology , 5: 462– 469. Spiezia, M.C., C. Chiarabelli, M.E. Schininà , and F. Polticelli, 2013. Bioactive Peptides from the Venom of the Mediterranean Cone Snail  Conus ventricosus. Nova Science Publishers Inc, pp. 135– 148. Spinella, A., L.A. Alvarez, and G. Cimino, 1993. Predator– prey relationship between Navanax inermis  and Bulla gouldiana : A chemical approach. Tetrahedron , 49: 3203– 3210. Sprung, M., 1983. Reproduction and fecundity of the mussel, Mytilus edulis  at Helgoland (North sea). Helgolä nder Meeresuntersuchungen , 36: 243– 255.

References Sreejamole, K.L., and C.K. Radhakrishnan, 2013. Antioxidant and cytotoxic activities of ethyl acetate extract of the Indian green mussel Perna viridis . Asian Journal of Pharmaceutical and Clinical Research , 6: 197– 201. Sreejamole, K.L., and C.K. Radhakrishnan, 2016. In vitro antioxidant activity of tissue extracts of green mussel Perna viridis . Journal of the Marine Biological Association of India , 58: 93– 98. Sri Kumaran, N., S. Bragadeeswaran, and S. Thangaraj, 2011. Screening for antimicrobial activities of marine molluscs Thais tissoti  (Petit, 1852) and Babylonia spirata  (Linnaeus, 1758) against human, fish and biofilm pathogenic microorganisms. African Journal of Microbiology Research , 5: 4155– 4161. Stephen, D., 1980. The reproductive biology of the Indian oyster Crassostrea madrasensis (Preston), 1: Gametogenic pattern and salinity. Aquaculture, 21: 139–146. Suarez-Jimenez, G., A. Burgos-Hernandez, and J. Ezquerra-Brauer, 2012. Bioactive peptides and depsipeptides with anticancer potential: Sources from marine animals. Marine Drugs , 10: 963– 986. Subavathy, P., A.U. Maheswari, R.D. Thilaga, J.H.J. Diaz, 2015. Assessment of in vitro anticancer activity of the marine gastropod Cypraea arabica  (L.1758). International Journal of Advance Research , 3: 20– 28, Subhapradha, N., P. Ramasamy, P. Seedevi, V. Shanmugam, A. Srinivasan, and A. Shanmugam, 2014. Extraction, characterization and its antioxidant efficacy of polysaccharides from Sepia aculeata  (Orbigny, 1848) cuttlebone. African Journal of Biotechnology , 13: 138– 144. Subhapradha, N., P. Ramasamy, and A. Srinivasan, 2013a. Preparation of chitosan derivatives from gladius of squid Sepioteuthis lessoniana  (Lesson, 1830) and antimicrobial potential against human pathogens. Journal of Biological Sciences , 13: 257– 263. Subhapradha, N., P. Ramasamy, S. Sudharsan, P. Seedevi, M. Moovendhan, D. Dharmadurai, S.V. Kumar, S. Vairamani, and A. Shanmugam, 2013b. Antioxidant potential of crude methanolic extract from whole body tissue of Bursa spinosa  (Schumacher, 1817). Proceedings of the National ConferenceUSSE , pp. 163– 167. Subhapradha, N., S. Suman, P. Ramasamy, R. Saravanan, V. Shanmugam, A. Srinivasan, and A. Shanmugam, 2013c. Anticoagulant and antioxidant activity of sulfated chitosan from the shell of donacid clam Donax scortum  (Linnaeus, 1758). International Journal of Nutrition, Pharmacology, Neurological Diseases , 3: 39– 45. Suhnel, S., F. Lagreze, J.F. Ferreira, L.H. Campestrini, and M. Maraschin, 2009. Carotenoid extraction from the gonad of the scallop Nodipecten nodosus  (Linnaeus, 1758) (Bivalvia: Pectinidae). Brazilian Journal of Biology , 69: 209– 215. Suja, N., and P. Muthiah, 2007. The reproductive biology of the baby clam, Marcia opima, from two geographically separated areas of India. Aquaculture, 273: 700–710. Suleria, H.A.R., P.P. Masci, R. Addepalli, W. Chen, G.C. Gobe, and S.A. Osborne, 2017. In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra ) viscera hydrolysate. Analytical and Bioanalytical Chemistry , 409: 4195– 4205. Sundaram, S., 2014. Fishery and biology of Sepia pharaonis  (Ehrenberg, 1831) off Mumbai, northwest coast of India. Journal of the Marine Biological Association of India , 56: 43– 47. Sunila, G., and K.Y.M. Salih, 2000. Studies on the biology of the wedge clam Donax incarnatus (Gmelin) from the Malippuram beach of Kerala. Cochin University of Science & Technology, http: //dyu thi.cusat. ac.in /xmlui/purl/2074.

187 Suntornchashwej, S., K. Suwanborirux, K. Koga, and M. Isobe, 2007. Malyngamide X: The first (7R)‐ lyngbic acid that connects to a new tripeptide backbone from the Thai sea hare Bursatella leachii . Chemistry— An Asian Journal , 2: 114– 122. Suresh, M., S. Arularasan, and N. Sri Kumaran, 2012. Screening on antimicrobial activity of marine gastropods Babylonia zeylanica  (Bruguiè re, 1789) and Harpa conoidalis (Lamarck, 1822) from Mudasalodai, southeast coast of India. International Journal of Pharmacy and Pharmaceutical Sciences , 4: 552– 556. Switzer-Dunlap, M., and M.G. Hadfield, 1977. Observations on development, larval growth and metamorphosis of four species of aplysiidae  (gastropoda: Opisthobranchia) in laboratory culture. Journal of Experimental Marine Biology and Ecology , 29: 245– 261. Tamari, M., and M. Kandatsu, 1986. Occurrence of ceramide aminoethylphosphonate in edible shellfish, AGEMAKI, Sinonovacula constricta . Agricultural and Biological Chemistry , 50: 1495– 1501. Tan, T.L., I. Paul-Pont, O.M. Evans, D. Watterson, P. Young, R. Whittington, A. Fougerouse, H. Bichet, A.C. Barnes, C. Dang, 2015. Resistance of black-lip learl oyster, Pinctada margaritifera , to infection by Ostreid herpes virus 1μ var under experimental challenge may be mediated by humoral antiviral activity. Fishand Shellfish Immunology , 44: 232– 240. Tan, Y., J. Xing, and W. Zhan, 2013. Agglutination activities of haemolymph and tissue extracts in scallop Chlamys farreri  and purification of mannan-binding lectin from haemolymph. Aquaculture , 400– 401: 148– 152. Tanaka, J., and T. Higa, 1999. Two new cytotoxic carbonimidic dichlorides from the nudibranch Reticulidia fungia . Journal of Natural Products , 62: 1339– 1340. Teshima, S., A. Kanazawa, and T. Ando, 1971. Occurrence of desmosterol and other sterols in the clam, Tapes philippinarum . Memoirs of the Faculty of Fisheries, Kagoshima University , 20: 131– 139. Tinoco-Orta, G.D., J. Cá ceres-Martı ́ nez, 2003. Infestation of the clam Chione fluctifraga  by the burrowing worm Polydora  sp. nov. in laboratory conditions. Journal of Invertebrate Pathology , 196– 205. Tringali, C., 2003. Bioactive Compounds from Natural Sources: Isolation, Characterization and Biological Properties . CRC Press, 693 p. Troncone, L., P. Gianluca, and A. Di Cosmo, 2012. Identification of the antimicrobial activity from Octopus vulgaris  haemocytes. https​://ww​w.iri​s.uni​na.it​/ hand​le/11​588/5​08049​#.WtR​oO9Ru​ bIU. Umayaparvathi, S., M. Arumugam, S. Meenakshi,G.Drä ger, A. Kirschning, and T. Balasubramanian, 2014. Purification and characterization of antioxidant peptides from oyster (Saccostrea cucullata ) hydrolysate and the anticancer activity of hydrolysate on human colon cancer cell lines. International Journal of Peptide Research and Therapeutics , 20: 231– 243. van Wyk, A.W., C.A. Gray, C.E. Whibley, O. Osoniyi, D.T. Hendricks, M.R. Caira, M.T. Davies-Coleman, 2008. Bioactive metabolites from the South African marine mollusk Trimusculus costatus . Journal of Natural Products , 71(3): 420– 425. Vasskog, T., J.H. Andersen, E. Hansen, and J. Svenson, 2012. Characterization and cytotoxicity studies of the rare 21: 4n-7 acid and other polyunsaturated fatty acids from the marine opisthobranch Scaphander lignarius , isolated using bioassay guided fractionation. Marine Drugs , 10: 2676– 2690. Velayutham, S., R.M. Sivaprakasam, S.F. Williams, and R. Samuthirapandian, 2014. Potential activity of in vitro antioxidant on methanolic extract of Babylonia zeylanica 

188 (Bruguiè re, 1789) from Mudasalodai, southeast coast of India. International Journal of Pharmacy and Pharmaceutical Science Research , 4: 60– 64. Venkatesan, V., R. Saravanan, S. Meenakshi, S. Umayaparvathi, and T. Umakalaiselvi, 2014. Antibacterial activity in the extracts of accessory nidamental gland of the Palk Bay squid Sepioteuthis lessoniana  (Lesson, 1830) (Cephalopoda: Decapoda). Indian Journal of Fisheries , 61: 146– 148. Vimala, P., and R.D. Thilaga, 2012. Antibacterial activity of the crude extract of a gastropod Lambis lambis  from the Tuticorin Coast, India. World Applied Sciences Journal , 16: 1334– 1337. Vo, T., and S. Kim, 2010. Potential anti-HIV agents from marine resources: An overview. Marine Drugs , 8: 2871– 2892. Wakimoto, T., K.C. Tan, and I. Abe. Ergot alkaloid from the sea slug Pleurobranchus forskalii  . https​://ww​w.jov​e.com ​/visu​alize​/ abst​ract/​23770​424/e​rgot-​alkal​oid-f​rom-t​he-se​a-slu​g-ple​urobr​ anchu​s-for​skali​i. Wang, L., H. Wu, N. Chang, and K. Zhang, 2011. Anti-hyperglycemic effect of the polysaccharide fraction isolated from Mactra veneriformis . Frontiers of Chemical Science and Engineering , 5: 238– 244. Wang, Y., H. He, G. Wang, H. Wu, B. Zhou, X.X. Chen, and Y. Zhang, 2010. Oyster (Crassostrea gigas ) hydrolysates produced on a plant scale have antitumor activity and immunostimulating effects in Balb/c mice. Marine Drugs , 8: 255– 268. Wen, L., S. Yang, H. Qiao, Z. Liu, W. Zhou, Y. Zhang, and P. Huang, 2005. SO‐ 3, a new O‐ superfamily conopeptide derived from Conus striatus  , selectively inhibits N‐  type calcium currents in cultured hippocampal neurons. British Journal of Pharmacology , 145: 728– 739. White, A.M., A.S. Dewia, K.L. Cheneyb, A.E. Winters, J.T. Blanchfield, and M.J. Garson, 2016. Oxygenated diterpenes from the Indo-Pacific nudibranchs Goniobranchus splendidus  and Ardeadoris egretta . Natural Product Communications , 11: 883– 1056. White, A.M., G.K. Pierens, T. Skinner-Adams, K.T. Andrews, P.V. Bernhardt, E.H. Krenske, E. Mollo, and M.J. Garson, 2015. Antimalarial isocyano and isothiocyanato sesquiterpenes with tri- and bicyclic skeletons from the nudibranch Phyllidia ocellata . Journal of Natural Products , 78: 1422– 1427. Widyastuti, A., L.P. Aji, 2016. Some aspects of reproduction in conch Lambis lambis  of Yenusi Coastal waters. Oseanologi dan Limnologi di Indonesia , 1: 1– 9. Wikarta, J.M., and S.M. Kim, 2016. Nitric oxide synthesis inhibition and cytotoxicity of Korean horse mussel Modiolus modiolus  extracts on cancer cells in culture. Cytotechnology , 68: 879– 890. Wikipedia— Littoraria angulifera . Williams, D.E., and R.J. Aandersen, 1987. Terpenoid metabolites from skin extracts of the dendronotid nudibranch Tochuina tetraquetra . Canadian Journal of Chemistry , 65: 2244– 2247. Wright, A.D., 2003. GC-MS and NMR analysis of Phyllidiella pustulosa  and one of its dietary sources, the sponge Phakellia carduus . Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology , 134: 307– 313. Wu, J., and S. Xu, 2015. In vivo antitumor activity of Meretrix meretrix  glycopeptide. International Conference on Applied Science and Engineering Innovation , 2015: 2162– 2166.

References Wu, X., H. Zhao, J. Che, R. Feng, C. Li, Z. Zhang, C. Zhang, G. Li, and Y. Zhao, 2014. The history and outlook of animal drugs treating asthma, chronic bronchitis, and haze episode– induced respiratory diseases. International Journal of Biotechnology for Wellness Industries , 3: 69– 78. Wu, Y., Y. Ma, L. Li, and X. Yang, 2018. Preparation and antioxidant activities in vitro of a designed antioxidant peptide from Pinctada fucata  by recombinant Escherichia coli . Journal of Microbiology and Biotechnology , 28: 1– 11. Wynsberge, S.V., S. Andréfouët, N. Gaertner-Mazouni, C.C.C. Wabnitz, M. Menoud, G. Le Moullac, P. Levy, A. Gilbert, and G. Remoissenet, 2017. Growth, Survival and Reproduction of the Giant Clam Tridacna maxima (Röding 1798, Bivalvia) in Two Contrasting Lagoons in French Polynesia. PLoS ONE 12: e0170565. Xu, J., Z. Chen, L. Song, L. Chen, J. Zhu, S. Lv, and R. Yu, 2013. A new in vitro anti-tumor polypeptide isolated from Arca inflata . Marine Drugs , 11: 4773– 4787. Yamakawa, A.Y., and H. Imai, 2012. Hybridization between Meretrix lusoria  and the alien congeneric species M. petechialis  in Japan as demonstrated using DNA markers. Aquatic Invasions , 7: 327– 336. Yuan, G., T. Yao, J. Li, Z. Zhang, and D. Li, 2007. Anti-inflammatory activity of the lipid extract of Mytilus crassitesta . Journal of Zhejiang University (Agric. & Life Sci.) , 33: 169– 173. Yuan, Q., L. Zhao, Q. Cha, Y. Sun, H. Ye, and X. Zeng, 2015. Structural characterization and immunostimulatory activity of a homogeneous polysaccharide from Sinonovacula constricta . Journal of Agricultural and Food Chemistry , 63: 7986– 7994. Yurimoto, T., Y. Mori, Y. Mori, S. Ito, Y. Maeno, 2008. Reproductive cycle of the subcrenated ark shell Scapharca kagoshimensis  (Tokunaga, 1906) in Ariake Bay, Japan. Journal of Shellfish Research , 27: 1101– 1108. Yusop, H.M., and M.F.S. Ramli, 2017. The study of Pholas orientalis ’ s life cycle and its relationship with the ecological parameters in states of Kedah, Perak and Selangor, Malaysia. IOSR Journal of Agriculture and Veterinary Science , 10: 15– 20. Zawadzki, M., C. Janosch, and J. Szechinski, 2013. Perna Canaliculus lipid complex PCSO524 demonstrated pain relief for osetoarthritis patients benchmarked against fish oil, a randomized trial, without placebo control. Marine Drugs, 11: 1920–1935. Zhang, L., and M. Koreeda, 2004. Total synthesis of (+)-acanthodoral by the use of a Pd-catalyzed metalene reaction and a nonreductive 5-exo-acyl radical cyclization. Organic Letters , 6: 537– 540. Zhang, D., H. Wu, Z. Xia, C. Wang, J. Cai, Z. Huang, L. Du, P. Sun, and J. Xie, 2012. Partial characterization, antioxidant and antitumor activities of three sulfated polysaccharides purified from Bullacta exarata . Journal of Functional Foods , 4: 784– 792. Zhu, B.W., L.S. Wang, D.Y. Zhou, D. Li, L. Sun, J. Yang, H. Wu, X. Zhou, and M. Tada, 2008. Antioxidant activity of sulphated polysaccharide conjugates from abalone (Haliotis discus hannai ). European Food Research and Technology , 227: 1663.

Index A Acanthella cavernosa, 161 Acanthella sp., 161 Acanthodoral, 155 Acanthodoris nanaimoensis, 155 A. carrageenovora, 10 Acetabularia, 117 Acetamide, 88 21-Acetoxydeoxoscalarin, 150 5-Acetoxypalisadin B, 126 Acetylelatol, 125 3-Acetyl-11-(3-methylbutanoyl)-13propanoylilikonapyron, 119 12-O-Acetyl-16-O-deacetyl-12,16episcalarolbutenolide, 150 Acinetobacter baumannii (A. baumannii), 17, 104 Acropora sp., 86 Actinocyclus papillatus, 155 Actisonitrile, 155 Activated partial thromboplastin time (APTT), 3, 30, 49 Acylglycerol, 87 Adalaria loveni, 155–156 Adenosine, 61 Aedes aegypti, 124 Aeromonas hydrophilla (A. hydrophila), 73, 75, 76, 79, 96, 97, 163 Aglajne-1, 59, 61 Aglajne-2, 59 Aglajne-3, 59 Agnewia tritoniformis, 77 Alcyonidium spp., 155 Alcyonium fauri, 158 Aldisa andersoni, 156 Allolaurinterol, 125 2Alpha,6beta,7alpha-triacetoxylabda-8,13 E-dien-15-ol, 52 3Alpha,11-dihydroxy-9,11-seco-cholest-4,7-dien6,9-dione, 52 Amphidinolide P, 140 Amphilectene, 161 Amphioctopus aegina, 173 AMPs, see Antimicrobial peptides (AMPs) Amusium pleuronectes, 26–27 Anadara antiquata, 4 Anadara broughtonii, 3 Anadara kagochimensis, 3–4 Anadara satowi, 4–5 Angasiol, 124 Anisodorin 1, 143 Anisodorin 2, 143 Anisodorin 3, 143 Anisodorin 4, 143 Anisodorin 5, 143 Anomalocardia flexuosa, 34 Antimicrobial peptides (AMPs), 10 Aplaminal, 130 Aplaminone, 129 Aplyolides A–E, 127 Aplyronine A, 128 Aplyronine B, 128 Aplyronine C, 128 Aplyronine D, 129

Aplyronine E, 129 Aplyronines F–H, 129 Aplyroseol-2, 148 Aplysia angasi, 123 Aplysia argus, 123–124 Aplysia dactylomela, 124–126 Aplysia depilans (A. depilans), 126–127 Aplysia fasciata, 127–128 Aplysia kurodai, 128–130 Aplysia oculifera, 130 Aplysia punctata (A. punctata), 131–132 Aplysiapyranoids A–D, 129 Aplysiasecosterol A, 130 Aplysiaterpenoid A, 130 Aplysiatoxin, 136 Aplysin, 129 Aplysina aerophoba (A. aerophoba), 122 Aplysinol, 129 Aplysistatin, 123, 126 Aplysqualenol A, 125 Aplysqualenol B, 126 Aplysulfurin, 148 Aplytandiene-3, 148 APTT, see Activated partial thromboplastin time (APTT) Arachidonic acid (ARA), 58 ARA, see Arachidonic acid (ARA) Archidoris montereyensis, 144 Argopecten ventricosus, 26 Armina babai (A. babai), 154 Artemia salina, 59 L-Ascorbic acid 2,6-dihexadecanoate, 36 Aspergillus flavus, 36, 167 Aspergillus fumigatus (A. fumigatus), 68, 77, 83 Aspergillus niger (A. niger), 36, 65, 77, 88, 95 Atactodea striata, 33 A. terreus, 83 Auriculol, 134 Aurilide, 134 Aurilide B, 134 Aurilide C, 134 Aurilol, 134 Auripyrone A, 135 Auripyrone B, 135 Auriside A, 134 Auriside B, 134 A. viridans, 10 Axinella, 161 Axinyssa, 161 Axisonitrile-3, 161 Axisothiocyanate-3, 161 Azumapecten farreri, 27

B Babylonia japonica, 96 Babylonia lutosa, 93 Babylonia spirata, 96–97 Babylonia zeylanica, 97 Bacillus cereus (B. cereus), 21, 55, 80, 83 Bacillus megaterium (B. megaterium), 10, 11, 42 Bacillus pumilus An 112, 3 Bacillus sp., 3

Bacillus subtilis (B. subtilis), 7, 46, 52, 60, 61, 69, 86, 87, 126, 167 Bathymodiolamides, 13 Bathymodiolus thermophilus, 12–13 Bedeva paivae (B. paivae), 77 1,4-Benzenediamine N-(1,3-dimethylbutyl)N’-phenyl, 91 1,2-Benzenedicaryboxylic acid, 5 6Beta,7alpha-diacetoxylabda-8,13 E-dien15-ol, 52 6Beta,7alpha,15-triacetoxylabda-8,13 E-diene, 52 Beta-carotene, 24 β-Sitosterol, 43 Bivalvia, 3–44 Branchipolynoe symmytilida, 13 Brassicasterol, 43 Bregmaceros sp., 165 Brentuximab vedotin (Adcetris®), 1, 2 Brianthein W, 159 Briareum violacea, 159 6-Bromo-4,5-dihydroxyindole, 86 6-Bromo-4,7-dihydroxyindole, 86 6-Bromo-5-hydroxyindole, 86 6-Bromoisatin, 87 Bryopsis pennata, 114 Bryopsis spp., 114, 115 Buccinum sp., 95 Buccinum undatum, 94 Bufonaria crumena (B. crumena), 63, 64 Bufonaria echinata, 63–64 Bufonaria rana, 64 Bugula dentata, 137 Bullacta exarata (B. exarata), 59–60 Bulla gouldiana (B. gouldiana), 59, 60 Bulla striata (B. striata), 58–59 Bursatella leachii, 122–123

C Cacospongia sp., 146 Caespitenone, 124 Caespitol, 125 Callista chione, 34 Campesterol, 43 Candida albicans (C. albicans), 6, 7, 31, 46, 65, 117 Candida sp., 167 Carbamic acid-methylene-di 4,1-phenylene bisdimethyl ester, 117 Carijoa riisei, 139 Carragelose, 1 Caryophyllene, 162 CAS, see Cyclohexasiloxane dodecamethyl (CAS) Caulerpa, 111, 117 Caulerpenyne, 113 C. drobachiensis, 10 Cellana grata (C. grata), 44 Cellana radiata, 45 Cellana toreuma, 45 Cephalopoda, 162–173 Cerastoderma edule (C. edule), 6

189

190 Cerithidea cingulata (C. cingulata), 55–56 Cerithidea obtusa, 56 Cerithium echinatum, 90 C. glabrata, 118 Chaetoceros sp., 8 Charonia lampas, 64 Chicoreus ramosus (C. ramosus), 88–89 Chicoreus sp., 89 Chicoreus virgineus, 89 Chionista fluctifraga, 34–35 Chlorella spp., 12 Chlorodesmin, 118 Chlorodesmis fastigiata, 118 (3Z,9Z)-7-chloro-6-hydroxy-12-oxo-pentadeca3,9-dien-1-yne, 128 Chlorolissoclimide, 120 9-Chloro-phorbazole D (20R)-Cholest-7,24-diene-3α,5α,6β,21-tetrol, 53 (20R)-Cholest-5,24-diene-3β,7β,21-triol, 53 (3β,5α) cholest-7-en-3-ol, 15 Cholesterol, 43 Cholest-7-en-3,5,7-triol, 52 Chromodoris, 147 Chromodoris annae, 149 Chromodoris aspersa, 150 Chromodoris elisabethina, 149 Chromodoris lochi (C. lochi), 150–151 Chromodoris quadricolor, 151 Chromodoris westraliensis, 149 Chromodorolide-A, 147 Chromodorolide-B, 147 Chthamalus scabrosus, 90 Clibanarius erythropus, 79 Coccomyxa parasitica (C. parasitica), 9 Codium tomentosum, 131 Concholepas concholepas, 90 Conus betulinus, 97–98 Conus bullatus (C. bullatus), 98 Conus consors, 99 Conus geographus, 99 Conus gloriamaris, 99 Conus inscriptus, 99 Conus kinoshitai, 100 Conus magus, 100 Conus marmoreus, 101 Conus miles, 101 Conus planorbis, 101 Conus purpurascens, 101–102 Conus radiatus, 102 Conus spp., 98 Conus stercusmuscarum, 102 Conus striatus, 102–103 Conus ventricosus, 103 Conus victoriae, 103 Corbicula japonica, 28 Cordyceps militaris mycelia (C. militaris mycelia), 49 Coriocella nigra, 70–71 Coscinodiscus, 3 C. parapsilosis, 117–118 Crassostrea gigas, 7 Crassostrea madrasensis, 18–19 Crassostrea rhizophorae, 19 Crassostrea virginica, 19–20 Crassotrea rhizophorae, 81 Crenomytilus grayanus (C. grayanus), 13 Crepidula fornicata, 65 Cryptococcus neoformans, 36 C-21 hydroxylated sterol, 53 Cupalaurenol, 125 Cyclina sinensis, 35

Index Cycloforskamide, 120 Cyclohexasiloxane dodecamethyl (CAS), 108 2-Cyclopentene-1-tridecanoic acid, 36 Cymbiola vespertilo (C. vespertilo), 93 Cymodocea nodosa, 6 Cypraea tigris, 65–66 Cytosar-U, 1

D Dactyloditerpenol acetate, 126 12-Deacetyl-18-epi-12-oxoscalaradial, 146 Deacetyl-dihydro-nor-thuridillanol, 111 12-Deacetyl-12-epi-scalaradial, 146 12-Deacetyl-12-oxoscalaradial, 146 Debromoaplysin, 129 Debromolaurinterol, 130 Debromolaurinterol acetate, 130 5,6-Dehydroaglane-3, 59 22-Dehydrocholesterol, 43 4'-N-demethyl-11-hydroxystaurosporine, 71 Dendrodoris fumata, 153 Dendrodoris limbata, 153–154 Dendrolasin, 151 Deodactol, 124 Deoxoscalarin-3-one, 150 Desacetylscalaradial, 146 Deschloroelatol, 125 Desmosterol, 43 D. gigas, 165 Diaulula sandiegensis, 152–153 Dicathais orbita, 87–88 Dichlorolissoclimide, 120 Didemnum sp., 23 Dihydro-nor-thuridillanol, 111 Dihydrosinularin, 54 Dihydrotochuinyl acetate, 140 3,11-Dihydroxystaurosporine, 71 ββ-Dimethylacryloylcholine, 81 1,1'-Dimethyl-[2,2']-bipyridyldiium salt, 34 17-(1,5-Dimethylhexy l)-10,13-dimethyl2,3,4,7,8,9,10,11,12,13,14,15,16,17tetradecahydro-1H-cyclopen ta[a] phenanthren-3-ol, 36 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 7, 17, 29, 40, 57, 64, 75, 84, 90, 91, 167 Diterpene 1, 149 Diterpene 2, 149 Diterpene 3, 149 Diterpene 4, 149 Diterpene 5, 149 2,4-Ditertbutylphenol, 91 4,7,10,13,16,19-Docosahexaenoic acid, 5 1-Docosanol, 91 Dolabelide A, 135 Dolabelide B, 135 Dolabelide C, 135 Dolabelide D, 135 Dolabella auricularia (D. auricularia), 132–135 Dolabellin, 135 Dolabrifera dolabrifera, 135–136 Dolastatin 1, 133 Dolastatin 3, 133 Dolastatin 10, 132 Dolastatin 11, 133 Dolastatin 12, 133 Dolastatin 13, 133 Dolastatin 14, 133 Dolastatin 15, 132 Dolastatin 16, 133 Dolastatin 17, 133

Dolastatin 18, 133 Dolastatin D, 133 Dolastatin G, 133 Dolastatin H, 133 Dolatriol, 132 Doliculide, 134 Donax cuneatus (D. cuneatus), 28–29 Donax faba, 29 Donax incarnatus, 29–30 Donax scortum, 30 Dorimidazole-A, 159 Dorisenone A, 148 Dorisenone B, 148 Dorisenone C, 148 Dorisenone D, 148 Doris fontainii, 142–143 Doris kerguelenensis (D. kerguelenensis), 143–144 Doryteuthis pealeii, 163 DPPH, see 2,2-Diphenyl-1-picrylhydrazyl (DPPH) Drupella fragum, 86 Drupella margariticola, 86–87

E Ectocarpus, 122 Edwardsiella tarda, 19 Eicosapentaenoic acid (EPA), 58 Elatol, 125 Elysia grandifolia (E. grandifolia), 112 Elysia nisbeti, 113 Elysia ornata, 113–114 Elysia patina (E. patina), 114 Elysia rufescens, 114–116 Elysia sp., 112 Elysia subornata, 116–117 Endoperoxide sterol, 127 Enterobacter aerogenes (E. aerogenes), 55, 56 Enterococcus faecalis (E. faecalis), 7, 10, 46, 84 Enterococcus viridans, 42 Enterococcus viridians, 11 Enteromorpha, 122 Enteromorpha intestinalis, 72 EPA, see Eicosapentaenoic acid (EPA) 3-Epi-aplykurodinone B, 128 Epibrasilenol acetate, 132 5a,8a-Epidioxycholest-6-en-3b-ol, 127, 136 5a,8a-Epidioxycholest-6-en-3b-ol, 131 5α,8α-Epidioxysterol, 131 4,5-Epi-10-isocyanoisodauc-6-ene, 161 Epinephrine-tetratms, 108 Epi-obtusane, 130 11-Epi-sinulariolide, 54 Epoxygoniolide-1, 148 Epoxylactone, 111 Ergosinine, 121 (3β,5α,22E)-ergosta-7,22-dien-3-ol, 15 Ergost-5-en-3-ol,(3a), 91 Erronea errones, 65 Escherichia coli (E. coli), 7, 10, 11, 17, 19, 31, 38, 39, 45, 46, 57, 60, 69, 73–75, 77, 79, 80, 82, 86–88, 90, 96, 97, 104, 105, 126, 163, 165, 167, 169, 171 Euchelus asper, 103–104 Euplacella cf. australis, 145 Euthria cornea (E. cornea), 55 Excavatolide C, 159

F Fauna, diversity of, 1 FDA, see Food and Drugs Administration (FDA)

191

Index FHCM, see Fungus Cordyceps militaris mycelia (FHCM) Ficus ficus, 67–68 Fissurella cumingi, 46 Fissurella latimarginata, 47 Fissurella maxima, 47 Flabellia petiolata, 111 Flavobacterium columnare, 69 Flora, diversity of, 1 F. moniliforme, 83 Food and Drugs Administration (FDA), 2 1-Formamido-10(1→2)-abeopupukeanane, 160 2-Formamidopupukeanane, 160 Fucus spp., 46 Fungus Cordyceps militaris mycelia (FHCM), 49 Furodysinin, 152 Fusarium spp., 68, 75

G Gafrarium divaricatum, 35–36 Galatea paradoxa, 7 Gambusia affinis, 59 Gastropoda, 44–162 Geloina expansa, 30–31 Geukensia demissa, 14 Glossodoris rufomarginata, 145–146 Goniobranchus cavae, 147 Goniobranchus obsoletus (G. obsoletus), 147–148 Goniobranchus splendidus, 148–149 Gracilin A, 149 Gracilin B, 149 Gracilin C, 149 Gracilin G, 149 Gracilin M, 149

H Haemonchus contortus (H. contortus), 147 Halaven, 1 Halgerda stricklandi, 152 Halichondria panacea, 153 Halichondria panicea, 142 Halichondria spp., 144, 161 Haliclona permollis, 153 Haliclona sp., 145 Haliclona spp., 144 Halimeda, 117 Halimeda kanaloana, 62, 130 Haliotis discus discus (H. discus discus), 48 Haliotis discus hannai (H. discus hannai), 48–49 Haliotis diversicolor (H. diversicolor), 49–50 Haliotis kamtschatkana (H. kamtschatkana), 48 Haliotis laevigata, 50 Haliotis rubra, 50–51 Haliotis rufescens, 51 Halocynthiaxanthin, 28 Haminoea virescens, 60 Hansenula anomala, 154 Harpago chiragra (H. chiragra), 69 Harpa major, 95 Hemifusus tuba, 93 Hemocyanin (Immucothel®), 2 Heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) (HTA), 58 Heparin, 24, 34 Hexadecanoic acid-ethyl ester, 117 1-Hexadecanol,2-methyl,1,2Benzenedicarboxylicacid, 91

n-Hexadecenoic acid, 5 Hexadecyl-glycerol, 144 Hexaplex trunculus (H. trunculus), 77–78 Hexobranchus sanguineus, 156–158 HGPEs, see Hypobranchial gland protein extracts (HGPEs) HTA, see Heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) (HTA) Hyatella sp., 151 6-Hydroxy-1-brasilene, 132 3β-Hydroxychlorolissoclimide, 120 21-Hydroxydeoxoscalarin, 150 10-Hydroxy,5,7-dimethoxy-2,3-dimethyl-1,4anthracene dione, 117 6β-Hydroxy-labda-8,13-dien-15-ol, 53 Hydroxyl-dehydroisofulvinol, 142 7α-Hydroxyspongian-16-One, 148 Hymedesmiidae, 156 Hypobranchial gland protein extracts (HGPEs), 78 Hypselodoris infucata, 152

I Ilikonapyrone esters (E–J), 119 Indigotin, 78 Inorolide A, 150 Inorolide B, 150 Inorolide C, 150 Isoacanthodoral, 155 Isochrysis galbana, 27 Isochrysis sp., 8 2-Isocyanoclovene, 161 3-Isocyanotheonellin, 161 Isodolastatin H, 133 Isofistularin-3, 122 Isoguanosine, 153 Isolaulimalide, 151 Isolaurenisol, 125 Isonaamidine A, 159 Isoparguerol, 126 Isopulo’unone, 59, 61 Isothiocyanatocyclohexane, 91 1-Isothiocyanatoepicaryolane, 161 10-Isothiocyano-4-cadinene, 161 3,19-Isovaleroyl-6,9-dihydroxylabda-8,17,13dien-15-oic acid, 53

J Jania capillacea, 67 Jorumycin, 145 Jorunna funebris, 145 Jorunnamycin A, 145 Jorunnamycin B, 145 Jorunnamycin C, 145

K Kahalalide A, 115 Kahalalide B, 115 Kahalalide C, 115 Kahalalide D, 115 Kahalalide E, 116 Kahalalide F, 113 Kahalalide G, 116 Kahalalide K, 116 Kahalalide R, 112 Kahalalide S, 112 Kahalalide V, 116 Kahalalide W, 116

Kahalalide X, 116 Kahalalide Y, 116 Kahalalide Z1, 114 Kahalalide Z2, 114 Kalihinol-A, 161 Kalihinol-E, 161 Keenamide A, 121 Kelletia kelletii, 94 Kelletinin E, 55 Kelletinin-I, 55, 94 Kelletinin-II, 94 Keyhole limpet hemocyanin (KLH), 48 Klebsiella aerogenes, 69 Klebsiella oxytoca (K. oxytoca), 39, 75 Klebsiella pneumoniae (K. pneumoniae), 7, 17, 23, 24, 38, 39, 46, 56, 69, 73, 75, 85, 88, 93, 96, 105, 118, 154, 163, 165, 167, 169, 171 Kuanoniamine A, 70 Kulokekahilide-1, 62, 63, 136 Kulokekahilide-2, 62, 137 Kulolide-1, 62 Kulolide-2, 63 Kulolide-3, 63

L Lactobacillus vulgaris, 75 Lambis lambis (L. lambis), 69 Lamellaria sp., 71 Lamellarin D, 71 Latrunculia magnifica, 154 Latrunculin A, 149 Latrunculin B, 149 Laulimalide, 151 Laurinterol, 130 Laurinterol acetate, 130 Leiosella levis, 151 Leishmania amazonensis, 124 Leishmania donovani, 127 Leminda millecra, 158 Leptogorgia palma, 158 Lessonia sp., 47 Lignarenone A, 58 Lignarenone B, 58 Listeria monocytogenes, 48 Listonella anguillarum, 95 Lithophaga teres, 14 Littorina littorea, 71–72 Littorina sitkana, 72 Lobatus gigas (L. gigas), 68 Lobophyton sp., 139 Loligo sp., 165–166 Loligo vulgaris, 164–165 Lovaza, 1 Lovenone, 156 L. pealeii, 163 Lunella coronata, 106–107 Lyngbya majuscula, 136 Lyngbyatoxin A, 137 Lyngbyatoxin A acetate, 137

M Mactra quadrangularis, 31–32 Mactromeris polynyma, 32 Makalika ester, 137 Makalikone ester, 137 Malyngamide O, 137 Malyngamide S, 123 Malyngamide X, 123

192 Marcia opima, 36–37 Margistrombus marginatus, 68 Marine mollusks, 1–2; see also individual entries approved drugs of, 2 constraints, 2 diversity of, 1 in US clinical cancer, 2 Marine natural products, 1 in pharmaceutical pipeline, 1 Marine pharmacology, present status of, 1 Marionia limceana, 140 Marmorofusus nicobaricus, 91 Mauritia arabica, 66 Megathura crenulata, 47–48 Melo melo (M. melo), 93 Membranipora membranacea, 155 Membrenone A, 121 Membrenone C, 121 Mercenaria campechiensis, 37 Mercenaria mercenaria, 37–38 Mercenene, 37 Meretrix casta, 38–39 Meretrix lusoria (M. lusoria), 39, 40 Meretrix meretrix, 39–40 Meretrix petechialis (M. petechialis), 40–41 Methoxyacetic acid,2-pentadecyl ester, 91 5-Methoxyindole-4,7-quinone, 86 6-Methoxyindole-4,7-quinone, 86 24-Methylenecholesterol, 43 1-Methylisoguanosine(doridosine), 142 N1-Methyl-phorbazole A, 156 2-Methylthio-3H-indol-3-one, 78 MGP0501, 40 Micrococcus luteus (M. luteus), 10, 11, 65, 95 Micrococcus lysodeikticus (M. lysodeikticus), 11, 42 Micrococcus sp., 67, 81 Millecrone A, 158 Millecrone B, 158 Millectrol B, 158 Minnivola pyxidata, 25–26 Modiolicola gracilicaudus, 12 Modiolus, 14–15 Molluskan-derived natural products, 1–2 Monetaria moneta, 66–67 M. tuberculosis, 91, 171 Mucor racemosus, 6, 171 Murex trapa, 79–80 Murex tribulus, 80 Mya arenaria (M. arenaria), 8–9 Mytilin, 10 Mytilus chilensis, 9 Mytilus edulis (M. edulis), 9–10 Mytilus galloprovincialis, 10–11, 78 Mytilus unguiculatus, 12 Myxilla, 153

N Nalodional, 58 Nanaimoal, 155 Navanax inermis (N. inermis), 60–61 Navenone A, 61 Navenone B, 61 Navenone C, 61 Navicula, 3 Nembrotha sp., 61 Neoaplaminone, 129 Neoaplaminone sulphate, 129 Nerita albicilla, 104

Index Neverita didyma, 74 N. gonarrhoeae, 84 Nidificene, 125 Nippostrongylus brasiliensis, 151 Nitzschia, 3 Niuhinone-B, 59 Nodipecten nodosus, 24 Nordolastatin G, 133 Nor-thuridillanol, 111 Notodoris gardineri, 158–159

O Obelia bidentata, 23 Oceanapia sp., 145 Ocenebra erinaceus, 78–79 9,12-Octadecadienoic acid(Z,Z), 91 Octadecamethylcyclononasiloxane, 108 Octadecane,2,2,4,15,17,17-hexamethyl-7, 12-bis(3,5,5-trimethylhexyl), 36 Octadecanoic acid-methyl ester, 117 Octopus cyaneus, 171–172 Octopus vulgaris, 172 Oculiferane, 130 Oiopatra sp., 68 Ommastrephes bartramii, 166 Onchidin, 119 Onchidin B, 119 Onchidione analogues (A–D), 119 Onchidium sp. (1), 118–119 Onchidium sp. (2), 119 Onchidium sp. (3), 119 Onchidium sp. (4), 119 Onchitriol I, 119 Onchitriol II, 119 Onuphis sp., 67 Ostrea edulis (O. edulis), 20 Oxazinin 1, 11 Oxazinin 2, 11 Oxazinin 3, 11 Oxazinin 4, 11 Oxymeris maculata, 92

P Pacifenediol, 125 Pacifenol, 125 Pacifidiene, 125 Paenibacillus, 3 Pagurus anachoretus, 79 P. alginovora, 10 Palisadins A, 126 Palmadorin A, 143 Palmadorin B, 143 Palmadorin C, 143 Palmadorin D, 143 Palmadorin M, 143 Palmadorin N, 143 Palmadorin O, 144 Para cresol, 88 Parasmittina parsevalii, 23 Paratapes undulatus, 41 Parguerol, 126 Paroctopus limaculatus, 173 Patella rustica, 45–46 Patella vulgata (P. vulgata), 46 Pectenol, 12 Peltodoris atromaculata, 141–142 Peltodoris nobilis, 142 Penaeus vannamei, 164 Penicillium expansum, 6, 171

Penicillium spp., 77, 88 Penicillus sp., 114 Pentadecanoic acid-14-methyl ester, 117 Permollis, 153 Perna canaliculus (P. canaliculus), 15–16 Perna viridis (P. viridis), 16–17 Peroniatriol I, 119 Peroniatriol II, 119 Perumytilus purpuratus, 90 Petrosia ficiformis, 141 P. fluorescens, 91 Phalium glaucum, 72–73 Phenol, 88 Phenol, 2,4-bis (1-phenylethyl), 5 Phidiana militaris, 141 Phidianidine A, 141, 142 Philinopsis depicta (P. depicta), 61 Philinopsis speciosa, 62–63 Pholas orientalis, 7–8 Phycothais reticulata, 85–86 Phyllidia coelestis, 160 Phyllidia ocellata, 160–161 Phyllidiella pustulosa, 161–162 Phyllodesmium briareum (P. briareum), 159 Phyllodesmium magnum (P. magnum), 159–160 Pinctada imbricata, 22 Pinctada imbricata fucata, 21–22 Pinctada margaritifera (P. margaritifera), 22–23 Pityrosporum ovale, 48 Plakobranchus ocellatus, 117–118 Planaxis sulcatus (P. sulcatus), 54 Planaxool, 54 Plasmodium falciparum, 162 Plasmodium falsiparum, 17 Pleurobranchus albiguttatus, 119–120 Pleurobranchus forskalii (P. forskalii), 120–121 Pleurobranchus membranaceus, 121 Pleuroploca trapezium, 90–91 Pleurosigma, 3 Pocillopora sp., 86 Polybrominated diphenyl ether, 126 Polydora sp., 35 Polygodial, 154 Polyhalogenated monoterpenes (1–3), 131 Porphyra sp., 72 Portunus pelagicus, 164 Preclathridine A, 159 Prenylated hydroquinone, 158 Protapes gallus, 41 Proteus mirabilis (P. mirabilis), 7, 19, 25, 38, 39, 70, 75, 154 Pseudomonas aeruginosa (P. aeruginosa), 7, 17, 19, 38, 46, 69, 77, 79, 80, 82, 84, 86, 88, 90, 104, 153, 154, 165, 167, 169 Pseudomonas sp., 3, 25, 154 Pteria avicular, 23 Pteria penguin, 23–24 Ptilosarcenone, 140 Ptilosarcone, 140 Ptychodera flava, 92 Pukalide, 140 1H-Purin-6-amine,[(2-fluorophenyl)methyl](CAS), 108 Purpura bufo, 82 Purpura persica, 82–83 P. vulgaris, 67, 69, 84, 89, 169 Pyrone 1, 118 Pyrone 2, 118 Pyura praeputialis, 46

193

Index R Ralfsia verrucosa, 51 Rapana bezoar, 83 Rapana rapiformis (R. rapiformis), 83–84 Rapana venosa, 84–85 Reishia clavigera, 85 Reticulidia fungia, 162 Reticulidin A, 162 Reticulidin B, 162 Retinoic acid, methyl ester, 117 Rhizopus sp., 167 Roboastra, 139 Rubifolide, 140 Ruditapes decussatus, 42 Ruditapes philippinarum, 42–43

S Saccharomyces cerevisiae, 154 Saccharothrix, 3 Saccostrea cucullata, 20–21 Saccostrea glomerata, 23 Salmonella abory, 67 Salmonella enteritidis, 100 Salmonella paratyphi (S. paratyphi), 23, 29, 39, 69, 73, 75–77, 79, 88, 95–97, 154 Salmonella pullorum (S. pullorum), 98, 100 Salmonella sp., 131, 169 Salmonella typhi (S. typhi), 19, 25, 38, 39, 46, 69, 73, 74, 79, 83, 88, 93, 96, 97, 154, 167 Sanguinamide B, 157 Sankha bhasma, 76 Sarcothelia edmonsoni, 139 Scalaradial, 146 Scaphander lignarius, 57–58 Schizothrix calcicola, 67 Scytonemin, 1 Scytosiphon lomentaria, 51 S. dysentriae, 89 Secosterol, 52 Semimytilus algosus, 90 Semiricinula tissoti, 81–82 Sepia aculeata, 166–167 Sepia brevimana, 167 Sepia esculenta, 167–168 Sepia kobiensis, 168–169 Sepia officinalis, 169–170 Sepia pharaonis (S. pharaonis), 170 Sepiella inermis (S. inermis), 170–171 Sepioteuthis lessoniana, 162–163 Sesquiterpenoid congeners, 160 Sessibugula translucens, 138 Shigella dysentreae, 25 Shigella flexneri (S. flexneri), 69, 83, 91, 118 Shigella sp., 29, 167 Sinonovacula constricta, 33 Sinularia densa, 139 Siphonaria diemensis, 51–52 Skeletonema sp., 8 Smaragdinella calyculata, 58 Soblidotin, 135 Sphingomonas, 3 Spisulosine, 32 Spondylus varius, 27–28 Staphylococcus aureus (S. aureus), 7, 10, 19, 25, 31, 38, 39, 45, 46, 52, 55, 60, 65, 69, 73–80, 82, 85, 86, 88, 90, 96–98, 105, 118, 126, 131, 153, 154, 163, 165, 167, 169, 171

Staphylococcus epidermidis (S. epidermidis), 23, 25 Staphylococcus sp., 131 Stigmasterol, 43 Stragulum bicolor, 140 Stramonita floridana, 80–81 Streptococcus mutans, 89 Streptococcus pneumoniae (S. pneumoniae), 7, 25, 39, 46, 105, 163, 169, 171 Streptococcus pyrogenes (S. pyrogenes), 65, 84 Streptococcus sp., 74, 169, 171 Streptomyces griseus, 163 Strombus canarium, 93 Stylocheilus longicauda, 136–137 Stylocheilus sp., 137 Stylocheilus striatus, 62 S. typhimurium, 7, 87, 98 Sunetta scripta, 43–44 Symbiodinium microadriaticum, 7 Synthadotin, 135

Trochus radiatus, 106 Trypanosoma cruzi, 124 Turbinella pyrum, 76–77 Turbo bruneus (T. bruneus), 107–108 Turbo marmoratus, 108–109 Turbo setosus, 109 Turbostatin 1, 110 Turbostatin 2, 110 Turbostatin 3, 110 Turbostatin 4, 110 Turbo stenogyrus, 109–110 Turbotoxin A, 109 Turbotoxin B, 109 Turritella acutangula, 53–54 Turritella attenuata (T. attenuata), 54 Tylodina perversa, 122 Tylothais savignyi, 80 Tyrannodoris tigris, 138–139 Tyrindoleninone, 87 Tyriverdin, 88

T

U

Tambja abdere, 139 Tambja ceutae, 137–138 Tambja eliora, 138 Tambjamine A, 138, 139 Tambjamine B, 138, 139 Tambjamine C, 139 Tambjamine D, 138, 139 Tambjamine K, 138 TBT, see Tributyltin (TBT) Tectus niloticus, 104–105 Tectus tentorium, 105 Tegillarca granosa (T. granosa), 5 Tegillarca rhombea, 6 Tegula gallina, 105–106 Telescopium telescopium (T. telescopium), 56–57 Tenguella marginalba, 89–90 Terebra argus, 92 Terebra consobrina, 92–93 Therapeutic properties, of marine-derived natural products, 1 Thunnus alalunga, 172 Thunnus albacares, 163 Thuridilla hopei, 111 Thuridilla splendens, 112 Thuridillin A, 111 Thuridillin B, 111 Thuridillin C, 111 Thyrsiferol, 124 Tibia curta, 70 Tisotumab Vedotin (HuMax®-TF-ADC), 135 Tivela mactroides, 44 Tochuina tetraquetra, 139–140 Tochuinyl acetate, 140 22-Trans-24-norcholesta-5,22-dien-3β-ol, 43 2,4,5-Tribromo-1H-imidazole, 78, 79 Tributyltin (TBT), 81 Trichoderma sp., 8, 83 Trichophyton mentagarophytes, 93 Trichostrongylus colubriformis (T. colubriformis), 147 Tridacna gigas, 7 Tridacna maxima, 6–7 Tridacna sp., 7 Trimusculus costatus, 52 Trimusculus peruvianus, 53 Tritoniopsin A, 139 Tritoniopsis elegans, 139

Udotea, 117 Ulapualide A, 157 Ulapualide B, 157 Ulapualide C, 157 Ulapualide D, 157 Ulapualide E, 157 Ulva lactuca (U. lactuca), 72 Ulva sp., 50 Ulvophyceae sp., 114 Unedogemmula indica, 76 Uroteuthis duvaucelii (U. duvaucelii), 164 U. vestiarum, 74

V Venustatriol, 125 Vibrio alginolyticus (V. alginolyticus), 9, 15, 169, 173 Vibrio anguillarum (V. anguillarum), 11, 65, 163, 173 Vibrio cholerae (V. cholerae), 17, 39, 56, 69, 73, 75, 76, 79, 87, 96, 97, 105, 154, 163, 167, 169, 171, 173 Vibrio harveyi (V. harveyi), 19, 45, 173 Vibrio ichthyoenteri, 48 Vibrio parahemolyticus (V. parahemolyticus), 39, 73, 75, 76, 79, 96, 97, 167, 169, 173 Vibrio splendidus, 11 Villorita cyprinoides, 31 Vira-A, 1 Volegalea cochlidium, 74–75, 75–76

X Xenophora mekranensis, 73 Xenophora sp., 73 Xestospongia sp., 145

Y Yondelis, 1

Z Zalypsis®, 145 Ziconotide (Prialt®), 1, 2 Zostera noltii, 6, 59