P. Gopalakrishnakone Editor-In-Chief Anita Malhotra Editor Evolution of Venomous Animals and Their Toxins Toxinology

Total Page:16

File Type:pdf, Size:1020Kb

P. Gopalakrishnakone Editor-In-Chief Anita Malhotra Editor Evolution of Venomous Animals and Their Toxins Toxinology Toxinology P. Gopalakrishnakone Editor-in-Chief Anita Malhotra Editor Evolution of Venomous Animals and Their Toxins Toxinology Editor-in-Chief P. Gopalakrishnakone In recent years, the field of toxinology has expanded substantially. On the one hand it studies venomous animals, plants and micro organisms in detail to understand their mode of action on targets. On the other hand, it explores the biochemical compo- sition, genomics and proteomics of toxins and venoms to understand their three interaction with life forms (especially humans), development of antidotes and exploring their pharmacological potential. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy and pharmacology. In addition, there is a fast-developing applied subfield, clinical toxinology, which deals with under- standing and managing medical effects of toxins on human body. Given the huge impact of toxin-based deaths globally, and the potential of venom in generation of drugs for so-far incurable diseases (for example, diabetes, chronic pain), the contin- ued research and growth of the field is imminent. This has led to the growth of research in the area and the consequent scholarly output by way of publications in journals and books. Despite this ever-growing body of literature within biomedical sciences, there is still no all-inclusive reference work available that collects all of the important biochemical, biomedical and clinical insights relating to toxinology. Composed of 12 volumes, Toxinology provides comprehensive and authoritative coverage of the main areas in toxinology, from fundamental concepts to new developments and applications in the field. Each volume comprises a focused and carefully chosen collection of contributions from leading names in the subject. Series Titles 1. Biological Toxins and Bioterrorism 2. Clinical Toxinology in the Asia Pacific and Africa 3. Spider Venoms 4. Scorpion Venoms 5. Marine and Freshwater Toxins 6. Venom Genomics and Proteomics 7. Snake Venoms 8. Evolution of Venomous Animals and Their Venoms 9. Microbial Toxins 10. Plant Toxins 11. Toxins and Drug Discovery 12. Clinical Toxinology in Australia, Europe, and Americas More information about this series at http://www.springer.com/series/13330 P. Gopalakrishnakone Editor-in-Chief Anita Malhotra Editor Evolution of Venomous Animals and Their Toxins With 89 Figures and 10 Tables Editor-in-Chief P. Gopalakrishnakone Venom and Toxin Research Programme Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore, Singapore Editor Anita Malhotra School of Biological Sciences Bangor University Bangor, Gwynedd, UK ISBN 978-94-007-6457-6 ISBN 978-94-007-6458-3 (eBook) ISBN 978-94-007-6459-0 (print and electronic bundle) DOI 10.1007/978-94-007-6458-3 Library of Congress Control Number: 2016962206 # Springer Science+Business Media Dordrecht 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer Science+Business Media B.V. The registered company address is: Van Godewijckstraat 30, 3311 GX Dordrecht, The Netherlands Series Preface The term TOXIN is derived from the Greek word Toeikov and is defined as a substance derived from tissues of a plant, animal, or microorganism that has a deleterious effect on other living organisms. Studying their detailed structure, function, and mechanism of action as well as finding an antidote to these toxins is the field of TOXINOLOGY, and the scientists are called TOXINOLOGISTS. In recent years, the field of toxinology has expanded substantially. On the one hand, it studies venomous animals, plants, and microorganisms in detail to under- stand their habitat, distribution, identification, as well as mode of action on targets, while on the other, it explores the biochemical composition, genomics, and proteo- mics of toxins and venoms to understand their interaction with life forms (especially humans), the development of antidotes, and their pharmacological potential for drug discovery. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy, pharmacology, etc. In addition, there is a fast developing applied subfield, clinical toxinology, which deals with understanding and managing medical effects of venoms and toxins on the human body following envenomations. Given the huge impact of envenomation-based deaths globally and the potential of venom in the generation of drugs for debilitating diseases (e.g., diabetes, chronic pain, and cancer), the continued research and growth of the field is imminent. Springer has taken the bold initiative of producing this series, which is not an easy target of producing about 12 volumes, namely, biological toxins and bioterrorism, clinical toxinology, scorpion venoms, spider venoms, snake venoms, marine and freshwater toxins, toxins and drug discovery, venom genomics and proteomics, evolution of venomous animals and their toxins, plant toxins, and microbial toxins. Singapore P. Gopalakrishnakone M.B.B.S., Ph.D., F.A.M.S., D.Sc. Editor-in-Chief v Acknowledgments I would like to sincerely thank the section editor of this volume, Anita Malhotra, for the invaluable contribution of her expertise and time and the authors who obliged with my request and provided a comprehensive review on the topics. Springer provided substantial technical and administrative help by many individ- uals at varying levels, but special mention should go to Sarah Mathews, Sunali Mull, Meghna Singh, Mokshika Gaur, and Audrey Wong for their tireless effort in bringing these volumes to reality. Singapore P. Gopalakrishnakone M.B.B.S., Ph.D., F.A.M.S., D.Sc. Editor-in-Chief vii Volume Preface Thomas Dobzhansky famously wrote “Nothing in Biology Makes Sense Except in the Light of Evolution” in his 1937 essay, a statement that firmly established evolution as a unifying concept in biology. To put it in another way, while classical toxinology investigated the “what” and “how” questions about animal toxins, the “why” questions involving the wider evolutionary context in which venomous animals developed was often overlooked. However, I am glad to say that this is no longer the case, and recent years have seen a free exchange of ideas between toxinologists and evolutionary biologists, with benefits to each field. Thus, this volume opens with a section containing chapters on the wider evolutionary context of venom in animals, the molecular evolu- tionary processes involved in generating diversity, and the concept of venom evolution as being driven by an arms race that also involves evolution of resistance to toxins by prey. As an evolutionary biologist, I am also strongly convinced that we can only study the evolution of toxins if it is underpinned by a clear understanding of the evolution of the animals that they evolved within. The original concept of the book was that a chapter on the evolution of venom and toxins within a particular group of venomous animals (Sect. 2) would be balanced by a chapter giving the latest understanding of the systematics of that group (Sect. 4). Our understanding of relationships changes all the time as new data or new methods of analysis become available, and the Handbook of Toxinology format is eminently suited to frequent updating. Finally, the volume finishes with a section of the evolution of venom delivery systems. The definition of a venomous animal, as opposed to a poisonous one, encompasses the evolution not just of toxins but also a specialized mechanism for administering them by injection. While venom delivery systems have been well studied in some groups, such as snakes, we are only just beginning to learn about the origins and amplification of these systems in other groups, such as centipedes. I am deeply grateful to the many authors who contributed to this volume for agreeing to share their expertise. I also wish to express my thanks to Professor Ponnampalam Gopalakrishnakone for inviting me to edit this volume and to the professional and patient editorial team at Springer (particularly Audrey Wong, Sunali Mull, and Sarah Mathews) for their support during the process. October 2016 Anita Malhotra Bangor, Gwynedd, UK B.A. (Oxon), Ph.D., F.L.S, F.R.S.B., F.Z.S.L ix Contents Part I The Wider Evolutionary Context ....................... 1 1 Evolutionary Context of Venom
Recommended publications
  • Tetrodotoxin
    Niharika Mandal et al. / Journal of Pharmacy Research 2012,5(7),3567-3570 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Tetrodotoxin: An intriguing molecule Niharika Mandal*, Samanta Sekhar Khora, Kanagaraj Mohanapriya, and Soumya Jal School of Biosciences and Technology, VIT University, Vellore-632013 Tamil Nadu, India Received on:07-04-2012; Revised on: 12-05-2012; Accepted on:16-06-2012 ABSTRACT Tetrodotoxin (TTX) is one of the most potent neurotoxin of biological origin. It was first isolated from puffer fish and it has been discovered in various arrays of organism since then. Its origin is still unclear though some reports indicate towards microbial origin. TTX selectively blocks the sodium channel, inhibiting action potential thereby, leading to respiratory paralysis. TTX toxicity is mainly caused due to consumption of puffer fish. No Known antidote for TTX exists. Treatment is symptomatic. The present review is therefore, an effort to give an idea about the distribution, origin, structure, pharmacol- ogy, toxicity, symptoms, treatment, resistance and application of TTX. Key words: Tetrodotoxin, Neurotoxin, Puffer fish. INTRODUCTION One of the most intriguing biotoxins isolated and described in the twentieth cantly more toxic than TTX. Palytoxin and maitotoxin have potencies nearly century is the neurotoxin, Tetrodotoxin (TTX, CAS Number [4368-28-9]). 100 times that of TTX and Saxitoxin, and all four toxins are unusual in being A neurotoxin is a toxin that acts specifically on neurons usually by interact- non-proteins. Interestingly, there is also some evidence for a bacterial bio- ing with membrane proteins and ion channels mostly resulting in paralysis.
    [Show full text]
  • Suppression of Potassium Conductance by Droperidol Has
    Anesthesiology 2001; 94:280–9 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Suppression of Potassium Conductance by Droperidol Has Influence on Excitability of Spinal Sensory Neurons Andrea Olschewski, Dr.med.,* Gunter Hempelmann, Prof., Dr.med., Dr.h.c.,† Werner Vogel, Prof., Dr.rer.nat.,‡ Boris V. Safronov, P.D., Ph.D.§ Background: During spinal and epidural anesthesia with opi- Naϩ conductance.5–8 The sensitivity of different compo- oids, droperidol is added to prevent nausea and vomiting. The nents of Naϩ current to droperidol has further been mechanisms of its action on spinal sensory neurons are not studied in spinal dorsal horn neurons9 by means of the well understood. It was previously shown that droperidol se- 10,11 lectively blocks a fast component of the Na؉ current. The au- “entire soma isolation” (ESI) method. The ESI Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/94/2/280/403011/0000542-200102000-00018.pdf by guest on 25 September 2021 thors studied the action of droperidol on voltage-gated K؉ chan- method allowed a visual identification of the sensory nels and its effect on membrane excitability in spinal dorsal neurons within the spinal cord slice and further pharma- horn neurons of the rat. cologic study of ionic channels in their isolated somata Methods: Using a combination of the patch-clamp technique and the “entire soma isolation” method, the action of droperi- under conditions in which diffusion of the drug mole- -dol on fast-inactivating A-type and delayed-rectifier K؉ chan- cules is not impeded by the connective tissue surround nels was investigated.
    [Show full text]
  • Biological Toxins Fact Sheet
    Work with FACT SHEET Biological Toxins The University of Utah Institutional Biosafety Committee (IBC) reviews registrations for work with, possession of, use of, and transfer of acute biological toxins (mammalian LD50 <100 µg/kg body weight) or toxins that fall under the Federal Select Agent Guidelines, as well as the organisms, both natural and recombinant, which produce these toxins Toxins Requiring IBC Registration Laboratory Practices Guidelines for working with biological toxins can be found The following toxins require registration with the IBC. The list in Appendix I of the Biosafety in Microbiological and is not comprehensive. Any toxin with an LD50 greater than 100 µg/kg body weight, or on the select agent list requires Biomedical Laboratories registration. Principal investigators should confirm whether or (http://www.cdc.gov/biosafety/publications/bmbl5/i not the toxins they propose to work with require IBC ndex.htm). These are summarized below. registration by contacting the OEHS Biosafety Officer at [email protected] or 801-581-6590. Routine operations with dilute toxin solutions are Abrin conducted using Biosafety Level 2 (BSL2) practices and Aflatoxin these must be detailed in the IBC protocol and will be Bacillus anthracis edema factor verified during the inspection by OEHS staff prior to IBC Bacillus anthracis lethal toxin Botulinum neurotoxins approval. BSL2 Inspection checklists can be found here Brevetoxin (http://oehs.utah.edu/research-safety/biosafety/ Cholera toxin biosafety-laboratory-audits). All personnel working with Clostridium difficile toxin biological toxins or accessing a toxin laboratory must be Clostridium perfringens toxins Conotoxins trained in the theory and practice of the toxins to be used, Dendrotoxin (DTX) with special emphasis on the nature of the hazards Diacetoxyscirpenol (DAS) associated with laboratory operations and should be Diphtheria toxin familiar with the signs and symptoms of toxin exposure.
    [Show full text]
  • Animal Venom Derived Toxins Are Novel Analgesics for Treatment Of
    Short Communication iMedPub Journals 2018 www.imedpub.com Journal of Molecular Sciences Vol.2 No.1:6 Animal Venom Derived Toxins are Novel Upadhyay RK* Analgesics for Treatment of Arthritis Department of Zoology, DDU Gorakhpur University, Gorakhpur, UP, India Abstract *Corresponding authors: Ravi Kant Upadhyay Present review article explains use of animal venom derived toxins as analgesics of the treatment of chronic pain and inflammation occurs in arthritis. It is a [email protected] progressive degenerative joint disease that put major impact on joint function and quality of life. Patients face prolonged inappropriate inflammatory responses and bone erosion. Longer persistent chronic pain is a complex and debilitating Department of Zoology, DDU Gorakhpur condition associated with a large personal, mental, physical and socioeconomic University, Gorakhpur, UttarPradesh, India. burden. However, for mitigation of inflammation and sever pain in joints synthetic analgesics are used to provide quick relief from pain but they impose many long Tel: 9838448495 term side effects. Venom toxins showed high affinity to voltage gated channels, and pain receptors. These are strong inhibitors of ion channels which enable them as potential therapeutic agents for the treatment of pain. Present article Citation: Upadhyay RK (2018) Animal Venom emphasizes development of a new class of analgesic agents in form of venom Derived Toxins are Novel Analgesics for derived toxins for the treatment of arthritis. Treatment of Arthritis. J Mol Sci. Vol.2 No.1:6 Keywords: Analgesics; Venom toxins; Ion channels; Channel inhibitors; Pain; Inflammation Received: February 04, 2018; Accepted: March 12, 2018; Published: March 19, 2018 Introduction such as the back, spine, and pelvis.
    [Show full text]
  • Saxitoxin and ,U-Conotoxins (Brain/Electric Organ/Heart/Tetrodotoxin) EDWARD MOCZYDLOWSKI*, BALDOMERO M
    Proc. Nati. Acad. Sci. USA Vol. 83, pp. 5321-5325, July 1986 Neurobiology Discrimination of muscle and neuronal Na-channel subtypes by binding competition between [3H]saxitoxin and ,u-conotoxins (brain/electric organ/heart/tetrodotoxin) EDWARD MOCZYDLOWSKI*, BALDOMERO M. OLIVERAt, WILLIAM R. GRAYt, AND GARY R. STRICHARTZt *Department of Physiology and Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45267-0576; tDepartment of Biology, University of Utah, Salt Lake City, UT 84112; and tAnesthesia Research Laboratories and the Department of Pharmacology, Harvard Medical School, Boston, MA 02115 Communicated by Norman Davidson, March 17, 1986 ABSTRACT The effect oftwo pL-conotoxin peptides on the 22 amino acids with amidated carboxyl termini (18). One of specific binding of [3H]saxitoxin was examined in isolated these toxins, GIIIA, has recently been shown to block muscle plasma membranes of various excitable tissues. pt-Conotoxins action potentials (18) and macroscopic Na current in a GITIA and GIHIB inhibit [3H]saxitoxin binding inlEkctrophorus voltage-clamped frog muscle fiber (19). At the single channel electric organ membranes with similar Kds of %50 x 10-9 M level, the kinetics of GIIIA block have been shown to in a manner consistent with direct competition for a common conform to a single-site binding model (Kd, 110 x 10-9 M at binding site. GITIA and GIIIB similarly compete with the 0 mV), from analysis of the statistics of discrete blocking majority (80-95%) of [3Hlsaxitoxin binding sites in rat skeletal events induced in batrachotoxin-activated Na channels from muscle with Kds of -25 and "140 x 10-9 M, respectively.
    [Show full text]
  • Evidence That Tetrodotoxin and Saxitoxin Act at a Metal Cation Binding Site in the Sodium Channels of Nerve Membrane (Solubilized Membrane/Receptors/Surface Charge) R
    Proc. Nat. Acad. Sci. USA 71 Vol. 71, No. 10, pp. 3936-3940, October 1974 Evidence That Tetrodotoxin and Saxitoxin Act at a Metal Cation Binding Site in the Sodium Channels of Nerve Membrane (solubilized membrane/receptors/surface charge) R. HENDERSON*, J. M. RITCHIE, AND G. R. STRICHARTZt Departments of Molecular Biophysics and Biochemistry, and of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510 Communicated by Frederic M. Richards, June 17, 1974 ABSTRACT The effects of monovalent, divalent, and STX. These experiments suggest how the toxins exert their trivalent cations on the binding of tetrodotoxin and saxi- toxin to intact nerves and to a preparation of solubilized action, and provide a unifying explanation of how several nerve membranes have been examined. All eight divalent cations affect nerve membrane permeability. and trivalent cations tested, and the monovalent ions MATERIALS AND LiW, Tl+, and H+ appear to compete reversibly with the METHODS toxins for their binding site. The ability of lithium to Tritium-labeled TTX and STX were prepared and purified reduce toxin binding is paralleled by its ability to reduce (3, 5). Olfactory nerves from garfish, obtained from the Gulf tetrodotoxin-sensitive ion fluxes through the nerve mem- brane. We conclude that the toxins act at a metal cation Specimen Co., Florida, were dissected by the method of binding site in the sodium channel and suggest that this Easton (12). A detergent-solubilized extract of the nerves site is the principal coordination site for cations (normally was prepared by the method of Henderson and Wang (4). Na+ ions) as they pass through the membrane during an Binding experiments were also carried out on intact garfish action potential.
    [Show full text]
  • Alcohol Dependence and Withdrawal Impair Serotonergic Regulation Of
    Research Articles: Cellular/Molecular Alcohol dependence and withdrawal impair serotonergic regulation of GABA transmission in the rat central nucleus of the amygdala https://doi.org/10.1523/JNEUROSCI.0733-20.2020 Cite as: J. Neurosci 2020; 10.1523/JNEUROSCI.0733-20.2020 Received: 30 March 2020 Revised: 8 July 2020 Accepted: 14 July 2020 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.jneurosci.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2020 the authors 1 Alcohol dependence and withdrawal impair serotonergic regulation of GABA 2 transmission in the rat central nucleus of the amygdala 3 Abbreviated title: Alcohol dependence impairs CeA regulation by 5-HT 4 Sophia Khom, Sarah A. Wolfe, Reesha R. Patel, Dean Kirson, David M. Hedges, Florence P. 5 Varodayan, Michal Bajo, and Marisa Roberto$ 6 The Scripps Research Institute, Department of Molecular Medicine, 10550 N. Torrey Pines 7 Road, La Jolla CA 92307 8 $To whom correspondence should be addressed: 9 Dr. Marisa Roberto 10 Department of Molecular Medicine 11 The Scripps Research Institute 12 10550 N. Torrey Pines Road, La Jolla, CA 92037 13 Tel: (858) 784-7262 Fax: (858) 784-7405 14 Email: [email protected] 15 16 Number of pages: 30 17 Number of figures: 7 18 Number of tables: 2 19 Number of words (Abstract): 250 20 Number of words (Introduction): 650 21 Number of words (Discussion): 1500 22 23 The authors declare no conflict of interest.
    [Show full text]
  • Dragon's Blood
    Available online at www.sciencedirect.com Journal of Ethnopharmacology 115 (2008) 361–380 Review Dragon’s blood: Botany, chemistry and therapeutic uses Deepika Gupta a, Bruce Bleakley b, Rajinder K. Gupta a,∗ a University School of Biotechnology, GGS Indraprastha University, K. Gate, Delhi 110006, India b Department of Biology & Microbiology, South Dakota State University, Brookings, South Dakota 57007, USA Received 25 May 2007; received in revised form 10 October 2007; accepted 11 October 2007 Available online 22 October 2007 Abstract Dragon’s blood is one of the renowned traditional medicines used in different cultures of world. It has got several therapeutic uses: haemostatic, antidiarrhetic, antiulcer, antimicrobial, antiviral, wound healing, antitumor, anti-inflammatory, antioxidant, etc. Besides these medicinal applica- tions, it is used as a coloring material, varnish and also has got applications in folk magic. These red saps and resins are derived from a number of disparate taxa. Despite its wide uses, little research has been done to know about its true source, quality control and clinical applications. In this review, we have tried to overview different sources of Dragon’s blood, its source wise chemical constituents and therapeutic uses. As well as, a little attempt has been done to review the techniques used for its quality control and safety. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Dragon’s blood; Croton; Dracaena; Daemonorops; Pterocarpus; Therapeutic uses Contents 1. Introduction ...........................................................................................................
    [Show full text]
  • Siteand Mechanism of Action of Resin Acids on Voltage-Gated Ion Channels
    Linköping University Medical Dissertation No. 1620 Site and Mechanism of Action of Resin Acids on Voltage-Gated Ion Channels Malin Silverå Ejneby Department of Clinical and Experimental Medicine Linköping University, Sweden Linköping 2018 © Malin Silverå Ejneby, 2018 Cover illustration: “The Charged Pine Tree Anchored to the Ground” was designed and painted by Daniel Silverå Ejneby. Printed in Sweden by LiU-Tryck, Linköping, Sweden, 2018 ISSN: 0345-0082 ISBN: 978-91-7685-318-4 TABLE OF CONTENTS ABSTRACT ............................................................................................................................... 1 POPULÄRVETENSKAPLIG SAMMANFATTNING ................................................................. 3 LIST OF ARTICLES .................................................................................................................. 5 INTRODUCTION ....................................................................................................................... 7 Ions underlie the electrical activity in the heart and brain .................................................. 7 A mathematical model for the nerve impulse - Hodgkin and Huxley ............................... 7 Cardiac action potentials – a great diversity of shapes ...................................................... 9 Voltage-gated ion channels ......................................................................................................... 9 General structure ....................................................................................................................
    [Show full text]
  • Tetrodotoxin
    TETRODOTOXIN O HO H O O N OH H2N H N HO OH OH Presentation by Neil Vasan Baran Lab Group Seminar August 13, 2003 TTX: Background • Toxic venom component of puffer fish or fugu (Spheroides rubripes), a Japanese delicacy (1 fish = ~$400) • First isolated in 1909 and named after puffer fish order Tetraodontidae • Structure first elucidated in 1964 by Woodward (confirmed by Kishi in 1965) • First synthesis by Kishi, et. al. in 1972 • Toxicity attributed to selective blockage of Na+ channels of skeletal muscles • Lethal dose for adult human = .001 mg • Upon ingestion, one feels tingling and lightheadedness but is lucid; paralysis and death ensue within 6-24 hours • 70-100 deaths each year, mostly in rural Japan • No known antidote exists 1 TTX: Structure O HO H O O N OH H2N H N HO OH OH O O O HO H O H OH O N N O H N OH 2 N H2N H HO H N HO OH OH OH OH Equilibrium mixture among ortho ester, anhydride, and lactone forms TTX: Kishi Synthesis Synthesis of Cyclohexane chiral core O O O H H Me , SnCl4 Me MsCl Me MeCN, rt Et N Me 3 (83%) (quant.) N O Me O Me O OH N OH N Ms H O OH H H H O o Me Me H Me H2O, 100 C NaBH4 m-CPBA Beckmann MeOH camphorsulfonic acidHO (96%) (75%) (61%) NH NH H NH O O O Ac Ac Ac 2 TTX: Kishi Synthesis Towards Tetrodamine H H H H H O O H O H Me H Me H Me 1) Al OCHMe2 3 HO (90% in 2 steps) O MPV-reduction O 2) H NH O NH O(COCH3)2, pyr.
    [Show full text]
  • Sea Anemone (Cnidaria, Anthozoa, Actiniaria) Toxins: an Overview
    Mar. Drugs 2012, 10, 1812-1851; doi:10.3390/md10081812 OPEN ACCESS Marine Drugs ISSN 1660-3397 www.mdpi.com/journal/marinedrugs Review Sea Anemone (Cnidaria, Anthozoa, Actiniaria) Toxins: An Overview Bárbara Frazão 1,2, Vitor Vasconcelos 1,2 and Agostinho Antunes 1,2,* 1 CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas 177, 4050-123 Porto, Portugal; E-Mails: [email protected] (B.F.); [email protected] (V.V.) 2 Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +351-22-340-1813; Fax: +351-22-339-0608. Received: 31 May 2012; in revised form: 9 July 2012 / Accepted: 25 July 2012 / Published: 22 August 2012 Abstract: The Cnidaria phylum includes organisms that are among the most venomous animals. The Anthozoa class includes sea anemones, hard corals, soft corals and sea pens. The composition of cnidarian venoms is not known in detail, but they appear to contain a variety of compounds. Currently around 250 of those compounds have been identified (peptides, proteins, enzymes and proteinase inhibitors) and non-proteinaceous substances (purines, quaternary ammonium compounds, biogenic amines and betaines), but very few genes encoding toxins were described and only a few related protein three-dimensional structures are available. Toxins are used for prey acquisition, but also to deter potential predators (with neurotoxicity and cardiotoxicity effects) and even to fight territorial disputes. Cnidaria toxins have been identified on the nematocysts located on the tentacles, acrorhagi and acontia, and in the mucous coat that covers the animal body.
    [Show full text]
  • A Review of Toxins from Cnidaria
    marine drugs Review A Review of Toxins from Cnidaria Isabella D’Ambra 1,* and Chiara Lauritano 2 1 Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy 2 Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-081-5833201 Received: 4 August 2020; Accepted: 30 September 2020; Published: 6 October 2020 Abstract: Cnidarians have been known since ancient times for the painful stings they induce to humans. The effects of the stings range from skin irritation to cardiotoxicity and can result in death of human beings. The noxious effects of cnidarian venoms have stimulated the definition of their composition and their activity. Despite this interest, only a limited number of compounds extracted from cnidarian venoms have been identified and defined in detail. Venoms extracted from Anthozoa are likely the most studied, while venoms from Cubozoa attract research interests due to their lethal effects on humans. The investigation of cnidarian venoms has benefited in very recent times by the application of omics approaches. In this review, we propose an updated synopsis of the toxins identified in the venoms of the main classes of Cnidaria (Hydrozoa, Scyphozoa, Cubozoa, Staurozoa and Anthozoa). We have attempted to consider most of the available information, including a summary of the most recent results from omics and biotechnological studies, with the aim to define the state of the art in the field and provide a background for future research. Keywords: venom; phospholipase; metalloproteinases; ion channels; transcriptomics; proteomics; biotechnological applications 1.
    [Show full text]