海洋毒素研究进展

摘要/Abstract

摘要：

从海洋生物中分离出大量结构新颖、生物活性独特的海洋毒素。本文对目前分离得到的海洋毒素进行了总结，包括：河豚毒素、麻痹性贝毒素、腹泻性贝毒素、肝脏毒贝毒素、神经性贝毒素、记忆丧失性贝毒素、西加毒素和其它类型的海洋毒素。海洋毒素不仅可以作为寻找新型防治心血管疾病药物和抗肿瘤药物的先导化合物，还是研究生命科学有用的工具。本文列出了67个重要的海洋毒素的结构并提供70篇参考文献。

关键词: 海洋毒素, 海洋代谢产物, 生物活性

Abstract:

A number of marine toxins with diverse structures and a wide array of fascinating bioactivities have been isolated from marine organism. Progress in the studies of marine toxins was summarized, including puffer fish poisoning, paralytic shellfish poisoning, azaspiracid shellfish poisoning, hepatotoxic shellfish poisoning, amnesic shellfish poisoning, diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, ciguatoxin and miscellaneous marine toxins. Marine toxins play a dominant role in the discovery of useful leads for the development of pharmaceutical agents for the treatment of diverse diseases like cancers, cardiovascular diseases, and central nervous system diseases and so on and also serve as useful tools to exploring biological sciences. Total 67 structures and 70 references were provided.

Key words: marine toxin, marine metabolite, bioactivity

中图分类号:

R284.2

李勇，杨雁，吴明，李力更，史清文. 海洋毒素研究进展[J]. 天然产物研究与开发, 2011, 23(3): 582-589.

LI Yong, YANG Yan, WU Ming, LI Li-geng, SHI Qing-wen. Progress in Marine Toxins[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2011, 23(3): 582-589.

参考文献 70

1	Al-Sabi A,McArthur J,Ostroumov V,et al.Marine toxins that target voltage-gated sodium channels.Mar Drugs,2006,4:157-192.
2	平田義正.天然物有机化学.东京:岩波书店,1981.1-308.
3	Noguchi T,Arakawa O.Tetrodotoxin-distribution and accumulation in aquatic organisms,and cases of human intoxication.Mar Drugs,2008,6:220-242.
4	Yasumoto T,Yotsu M,Murata M.New tetrodotoxin analogs from the newt Cynops ensicaudaJ Am Chem Soc,1988,110:2344-2345..
5	Llewellyn LE.Saxitoxin,a toxic marine natural product that targets a multitude of receptors.Nat Prod Rep,2006,23: 200-222.
6	McMahon,T,Silke J.Winter toxicity of unknown aetiology in mussels.Harmful Algae News,1996,14:2.
7	Satake M,Ofuji K,Naoki H,et al.Azaspiracid,a new marine toxin having unique spiro ring assemblies,isolated from Irish mussels,Mytilus edulis.J Am Chem Soc,1998,120,9967-9968.
8	Amzil Z,Sibat M,Royer F,et al.First report on azaspiracid and yessotoxin groups detection in French shellfish.Toxicon,2008,52:39-48.
9	James KJ,Sierra MD,Lehane M,et al.Detection of five new hydroxyl analogues of azaspiracids in shellfish using multiple tandem mass spectrometry.Toxicon,2003,41:277-283.
10	Ofuji K,Satake M,McMahon T,et al.Two analogs of azaspiracid isolated from mussels,Mytilus edulis,involved in human intoxication in Ireland.Nat Toxins,1999,7:99-102.
11	Ito E,Satake M,Ofuji K,et al.Multiple organ damage caused by a new toxin azaspiracid,isolated from mussels produced in Ireland.Toxicon,2000,38:917-930.
12	Campas M,Prieto-Simon B,Marty JL.Biosensors to detect marine toxins:Assessing seafood safety.Talanta,2007,72:884-895.
13	Kulagina NV,Twiner MJ,Hess P,et al.Azaspiracid-1 inhibits bioelectrical activity of spinal cord neuronal networks.Toxicon,2006,47:766-773.
14	Lee JS,Igarashi T,Fraga S,et al.Determination of diarrhetic shellfish toxins in various dinoflagellate species.J Appl Phycol,1989,1:147-152.
15	Terao K,Ito E,Oarada M,et al.Histopathological studies on experimental marine toxin poisoning.The effects in mice of yessotoxin isolated from Patinopecten yessoensis and of a desulfated derivative.Toxicon,1990,28:1095-1104.
16	Arias HR.Marine toxins targeting ion channels.Mar Drugs,2006,4:37-69.
17	Murata M,Masanori K,Lee JS,et al.Isolation and structure of Yessotoxin,a novel polyether compound implicated in diarrhetic shellfish poisoning.Tetrahedron Lett,1987,28:5869-5872.
18	Tubaro A,Dell’Ovo V,Sosa S,et al.Yessotoxins: A toxicological overview.Toxicon,2009,in press.
19	Perl TM,Bedard L,Kosatsky T,et al.An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid.N Engl J Med,1990,322:1775-1780.
20	Quilliam MA,Wright JL.The amnesic shellfish poisoning mystery.Anal Chem,1989,61:1053A-1106A.
21	Iverson F,Truelove J,Nera E,et al.Domoic acid poisoning and mussel-associated intoxication: preliminary investigations into the response of mice and rats to toxic mussel extract.Food Chem Toxicol,1989,27:377-384.
22	Perl TM,Teitelbaum J,Hockin J,et al.Domoic acid toxicity.Panel discussion: definition of the syndrome.Can Dis Wkly Rep,1990,16Suppl 1E:41-45.
23	Zatorre RJ.Memory loss following domoic acid intoxication from ingestion of toxic mussels.Can Dis Wkly Rep,1990,16 Suppl 1E:101-103.
24	Takemoto T,Daigo K.Recent developments in kainoid amino acid chemistry.Chem Pharm Bull,1958,6:578-583.
25	Impellizzeri G,Mangiafico S,Oriente G,et al.Amino acids and low-molecular-weight carbohydrates of some marine red algae.Phytochemistry,1975,14:1549.
26	Pulido O M.Domoic acid toxicologic pathology: A review.Mar Drugs,2008,6:180-219.
27	Tachibana K,Scheuer P,Tsukitani Y,et al.Okadaic acid,a cytotoxic polyether from two marine sponges of the genus Halichondria.J Am Chem Soc,1981,103:2469-2471.
28	Yasumoto T.Fish poisoning due to toxins of microalgal origins in the Pacific.Toxicon,1998,36:1515-1518.
29	Zhou J,Fritz L.Okadaic acid antibody localizes to chloroplasts in the DSP-toxin-producing dinoflagellates Prorocentrum lima and Prorocentrum maculosum.Phycologia,1994,33:455-461.
30	McLachlan JL,Boalch GT,Jahn R.Reinstatement of the genus Exuviaella (Dinophyceae,Prorocentrophycidae) and an assessment of Prorocentrum lima.Phycologia,1997,36:437-510.
31	Yasumota T,Murada M,Oshima Y.Diarrhetic shellfish toxins.Tetrahedron,1985,41:1019-1025.
32	Fernández JJ,Suárez-Gómez B,Souto ML.Identification of new okadaic acid derivatives from laboratory cultures of Prorocentrum lima.J Nat Prod,2003,66:1294-1296.
33	Cruz PG,Daranas AH,Fernández JJ.DTX5c,a new OA sulphate ester derivative from cultures of Prorocentrum belizeanum.Toxicon,2006,47:920-924.
34	Lin YY,Risk M,Ray SM.Isolation and structure of brevetoxin B from the “red tide” dinoflagellate Ptychodiscus brevis ( Gymnodinium breve ).J Am Chem Soc,1981,103:6773-6775.
35	Baden DG.Marine food-borne dinoflagellate toxins.Int Rev Cytol,1983,82:99-150.
36	Baden DG.Brevetoxins:unique polyether dinoflagellate toxins.FASEB J,1989,3:1807-1817.
37	Dechraoui MY,Naar J,Pauillac S,et al.Ciguatoxins and Brevetoxins,Neurotoxic Polyether Compounds Active on Sodium Channels.Toxicon,1999,37:125-143.
38	Bottein Dechraoui MY,Tiedeken JA,Persad R,et al.Use of two detection methods to discriminate ciguatoxins from brevetoxins: Application to great barracuda from Florida Keys.Toxicon,2005,46:261-270.
39	Murata M,Legrand AM,Ishibashi Y.Structures of ciguatoxin and its congener.J Am Chem Soc,1989,111:8929-8932.
40	Satake M,Morohashi A,Oguri H.The absolute configuration of ciguatoxin.J Am Chem Soc,1997,119:11325-11326.
41	Scheuer PJ.Ciguatera and its off-shoots-chance encouters en route to molecular structure.Tetrahedron,1994,50:3-18.
42	Lewis RJ,Vernoux JP,Brereton IM.Structure of Caribbean ciguatoxin isolated from Caranx latus.J Am Chem Soc,1998,120:5914-5920.
43	Lewis RJ.The changing face of ciguatera.Toxicon,2001,39:97-106.
44	Hamilton B,Hurbungs M,Jones A,et al.Multiple ciguatoxins present in Indian Ocean reef fish.Toxicon,2002,40: 1347-1353.
45	Hamilton B,Hurbungs M,Vernoux JP,et al.Isolation and characterisation of Indian Ocean ciguatoxin.Toxicon,2002,40:685-693.
46	Satake M,Murata M,Yasumoto T.Gambierol: A new toxic polyether compound isolated from the marine dinoflagellate Gambierdiscus toxicus.J Am Chem Soc,1993,115:361-362.
47	Murata M,Iwashita T,Yokoyama A.A cytochrome oxidase reactivity model: generation of a peroxo-bridged iron/copper dinuclear complexJ Am Chem Soc,1992,114:6594-6597..
48	Murata M,Yasumoto T.The structure elucidation and biological activities of high molecular weight algal toxins: maitotoxin,prymnesins and zooxanthellatoxins.Nat Prod Rep,2000,17:293-331.
49	Murata M,Yasumoto T.Marine toxins.Chem Rev,1993,93:1897-1909.
50	Gallimore AR,Spencer JB.Stereochemical uniformity in marine polyether ladders-implications for the biosynthesis and structure of maitotoxin.Angew Chem Int Ed,2006,45:4406-4416.
51	Nicolaou KC,Frederick MO.On the structure of maitotoxin.Angew Chem Int Ed,2007,46:5278-5282.
52	Li S,Wattenberg EV.Differential activation of nitrogenactived protein kinases by palytoxin and ouabain,two ligands for the Na1,K1 ATPase.Toxicol Appl Pharmacolg,1998,2:377-384.
53	Moore RE,Bartolini G.Structure of palytoxin.J Am Chem Soc,1981,103:2491-2494.
54	Uemura D,Hirata Y,Iwahita T.Studies on plytoxins.Tetrahedron,1985,41:1007-1017.
55	Kishi,Y.Palytoxin: an inexhaustible source of inspiration-personal perspective.Tetrahedron,2002,58:6239-6256.
56	Satake MI,Murata M,Yasumoto T,et al.Amphidinol,a polyhydroxypolyene antifungal agent with an unprecedented structure from a marine dinoflagellate,Amphidinium klebsii.J Am Chem Soc,1991,113:9859-9861.
57	Murata M,Matsuoka S,Matsumori N,et al.Absolute configuration of amphidinol 3,the first complete structure determination from amphidinol homologues:application of a new configuration analysis based on carbonhydrogen spin-coupling constants.J Am Chem Soc,1999,121:870-871.
58	Otofuji T,Ogo A,Koishi J,et al.Food Sanit Res,1981,31,76-83.
59	Uemura D,Chou T,Haino T,et al.A toxic amphoteric macrocycle from the Okinawan bivalve Pinna muricata.J Am Chem Soc,1995,117:1155-1156.
60	Chou T,Haino T,Kuramoto M,et al.Isolation and structure of pinnatoxin D,a new shellfish poison from the Okinawan bivalve Pinna muricata.Tetrahedron Lett,996,37:4027-4030.
61	Torigoe K,Murata M,Yasumoto T,et al.Prorocentrolide,a toxic nitrogenous macrocycle from a marine dinoflagellate,Prorocentrum lima.J Am Chem Soc,1988,110:7876-7877.
62	Hu T,de Freitas ASW,Curtis JM,et al.Isolation and structure of prorocentrolide B,a fast-acting toxin from Prorocentrum maculosum.J Nat Prod,1996,59:1010-1014.
63	Shumway SE.A review of the effects of algal blooms on shellfish and aquaculture.J World Aquacult Soc,1990,21: 65-104.
64	Molinski TF,Dalisay DS,Lievens SL,et al.Drug development from marine natural products.Nature Reviews,2009,9:70-85.
65	Garcia CF,Gallardo RJ,Sánchez MA,et al.Biotechnological significance of toxic marine dinoflagellates.Biotechnology Advances,2007,25,176-194.
66	Dubilier N,Bergin C,Lott C.Symbiotic diversity in marine animals: the art of harnessing chemosynthesis.Nature Reviews,2007,6:725-740.
67	Nicolaou KC,Frederick MO,Aversa RJ.The continuing saga of the marine polyether biotoxins.Angew Chem Int Ed,2008,47:7182-7225.
68	Hirama M.Total synthesis of ciguatoxin CTX3C:A venture into the problems of ciguatera seafood poisoning.The Chemical Record,2005,5:240-250.
69	Morrisa JC,Phillips AJ.Marine natural products: synthetic aspects.Nat Prod Rep,2009,26:245-265.
70	Inoue M,Miyazaki K,Uehara H,et al.First- and second-generation total synthesis of ciguatoxin CTX3C.PNAS,2004,101:12013-12018.

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