南海海绵Haliclona cymaeformis和Topsentia sp.化学成分及生物活性研究
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摘要
中国南海海洋生物中含有大量结构新颖且具有抗肿瘤、抗菌等活性的次生代谢产物,是寻找高效低毒药物或先导化合物的宝贵资源。
本研究依据海洋化学生态学的研究思路,结合海洋天然产物研究方法,研究中国南海蜂海绵属Haliclona cymaeformis和南海海绵Topsentia.sp.的化学成分和次级代谢产物的生物活性。运用正相硅胶、反相硅胶(ODS)和凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化;通过理化性质和波谱数据,结合文献对照,鉴定化合物的结构。从海绵H. cymaeformis的乙醇提取物中共分离鉴定了15个单体化合物:9-(4’-carbonypentan-2’(R)-yl)purine -6-hydroxy (1), 7-(4’-carbonypentan-2’-yl)purine-2-hydroxy(2), 7-(5’-carbonylpentan-3’-yl)purine -2-hydroxy (3), 7-(4’-carbonylpentan-2’-yl)purine -2-hydroxy (4), 24-亚甲基胆甾醇(5), 5α,8β-epidioxy-cholesta-6-en-3-ol (6), cholesta-7-en-3β,5α,6α,9α-tetraol (7),胆甾醇(8), 3-吲哚甲酸(9),尿嘧啶(10),胸腺嘧啶(11),尿嘧啶核苷(12),胸腺嘧啶核苷(13),尿嘧啶脱氧核苷(14)和胸腺嘧啶脱氧核苷(15),其中化合物1 ~ 4为新化合物,化合物5 ~ 15均首次从该海绵中分离得到。从海绵Topsentia .sp.的乙醇提取物中共分离得到22个化合物,鉴定了20个化合物,为Topsentiasterol (F-J) (16-20), (22E)-24-Isopropyl-22-dehydrocholesterol (21),胆甾醇(22), Hydroxy-(4-hydroxyphenyl)-acetic acid ethyl ester (23), diethyl 2,2'-(4,4'-oxybis(4,1-phenylene))bis(2-hydroxyacetate) (24),对羟基苯甲酸(25),甲基苯甲酸(26),间甲基苯甲酸(27), 3-吲哚甲酸(28), 1-(O-5,9,13-trimethyltetradecanoyl)-glycerol (29), 18-羟基硬脂酸(30), 1-O-cis-9-octadecenylglycerol (31), batyl alcohol (32), 7(Z),10(Z)-Hexadecadienoic acid (33),十八烷酸(34),β-D-吡喃岩藻糖乙二醇苷(35)。其中化合物16 ~ 20和24为新化合物,化合物23, 29, 35为新天然产物。
采用MTT法测定了其中20个化合物的细胞毒活性,结果表明,化合物7对慢性髓原白血病细胞(K562)和人肝癌细胞(SMMC-7721)的增殖显示了较强的生长抑制活性;化合物16对人白血病细胞(K562)和人胃癌细胞(SGC-7902)有较强的细胞毒活性;化合物17对人白血病细胞(K562)有较强的细胞毒活性。采用滤纸片扩散法测定了所有化合物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌(MRSA),白色念珠菌的生长抑制活性。只有化合物30对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌有较弱的抑制活性。还采用滤纸片扩散法测定了其中10个化合物对农业病原菌:辣椒疫霉(Phytophthora capsici)、瓜果腐霉(Pythium aphanidermatum)、钟器腐霉(Pythium vexans)和尖孢镰刀菌(Fusarium oxysporum f.sp. cubense)的生长抑制活性,但是没有发现活性。
The South China Sea is a rich resource of acquiring secondary metabolites of unique structure with various bioactivities such as anti–tubercular, anti-tumor, anti-virus,antibiosis, ,anti-inflammatory, anti-allergy, treatments for neurological disorders and osteoporosis, and immunomodulation.
According to the methodology of chemical ecology combining with modern technology of marine natural products, in this paper, study of the chemical constituents of the sponge Haliclona cymaeformis and Topsentia sp. which was collected from the South China Sea, was carried out. The compounds were isolated and purified by column chromatography on silica gel, reversed-phase silica gel (ODS) and Sephadex LH-20, and their structures were elucidated on the basis of physicochemical and sp.tral analysis. As a result, Fifteen compounds were isolated from the ethanol extract of H. cymaeformis, and their structures were identified as 9-(4’-carbonypentan-2’(R)-yl)purine-6-hydroxy(1), 7- (4’-carbonypentan-2’-yl)purine -2-hydroxy(2), 7-(5’-carbonylpentan-3’-yl)purine-2-hydroxy (3), 7- (4’- carbonylpentan-2’-yl)purine-2-hydroxy (4),24-methylene-cholesta-3β-ol (5), 5α,8β-epidioxy-cholesta-6-en-3-ol (6), cholesta-7-en-3β,5α,6β,9α-tetraol (7), cholesterol (8), 1H-indole-3-carboxylic acid (9), uracil (10), thymine (11), uridine (12), thymidine (13), 2'-deoxyuridine (14), and 2'-deoxythymidine (15), resp.tively. Compounds 1– 4 were new purine alkaloids, Compounds 5– 15 were obtained from the sponge H. cymaeformis for the first time. Moreover, twenty-two compounds were isolated from the ethanol extract of Topsentia sp., and twenty of their structures were identified as Topsentiasterol (F-J) (16-20) (22E)-24-Isopropyl-22-dehydrocholesterol (21), cholesterol (22), Hydroxy-(4-hydroxyphenyl)-acetic acid ethyl ester (23), diethyl 2,2'-(4,4'-oxybis(4,1-phenylene)) bis(2-hydroxyacetate) (24),4-Hydroxybenzoic acid (25), 4-Methylbenzoic acid (26), 2-Methylbenzoic acid (27), 1H-indole-3-carboxylic acid (28), 1-(O-5,9,13-trimethyltetradecanoyl)-glycerol (29), Octadecanoic acid (30), 1-O-cis-9-octadecenylglycerol (31), batyl alcohol (32), 7(Z),10(Z)-Hexadecadienoic acid (33), stearic acid (34),β-D-Fucoside-O-ethylene glycol (35)。Compounds 16– 20 and 24 were new compounds, compounds 23, 29, 35 were new natural products.
The cytotoxic activities was tested by MTT assay, Compounds 7 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) and human hepatoma (SMMC-7721) cell lines. Compounds 16 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) and human gastric carcinoma (SGC-7901) cell lines. Compounds 17 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) cell lines. The antimicrobial activities against Staphylococcus aureus, and Methicillin-resitant Staphylococcus aureus (MRSA), were measured using paper disco diffusion method. Consequently, only compound 30 showed weak inhibitory activity against both S. aureus and MRSA. The antimicrobial activities against Phytophthora capsiciPythium aphanidermatum, Pythium vexans,and Fusarium oxysporum f.sp. cubense were also tested, unfurturaly, no activity was found
本研究依据海洋化学生态学的研究思路,结合海洋天然产物研究方法,研究中国南海蜂海绵属Haliclona cymaeformis和南海海绵Topsentia.sp.的化学成分和次级代谢产物的生物活性。运用正相硅胶、反相硅胶(ODS)和凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化;通过理化性质和波谱数据,结合文献对照,鉴定化合物的结构。从海绵H. cymaeformis的乙醇提取物中共分离鉴定了15个单体化合物:9-(4’-carbonypentan-2’(R)-yl)purine -6-hydroxy (1), 7-(4’-carbonypentan-2’-yl)purine-2-hydroxy(2), 7-(5’-carbonylpentan-3’-yl)purine -2-hydroxy (3), 7-(4’-carbonylpentan-2’-yl)purine -2-hydroxy (4), 24-亚甲基胆甾醇(5), 5α,8β-epidioxy-cholesta-6-en-3-ol (6), cholesta-7-en-3β,5α,6α,9α-tetraol (7),胆甾醇(8), 3-吲哚甲酸(9),尿嘧啶(10),胸腺嘧啶(11),尿嘧啶核苷(12),胸腺嘧啶核苷(13),尿嘧啶脱氧核苷(14)和胸腺嘧啶脱氧核苷(15),其中化合物1 ~ 4为新化合物,化合物5 ~ 15均首次从该海绵中分离得到。从海绵Topsentia .sp.的乙醇提取物中共分离得到22个化合物,鉴定了20个化合物,为Topsentiasterol (F-J) (16-20), (22E)-24-Isopropyl-22-dehydrocholesterol (21),胆甾醇(22), Hydroxy-(4-hydroxyphenyl)-acetic acid ethyl ester (23), diethyl 2,2'-(4,4'-oxybis(4,1-phenylene))bis(2-hydroxyacetate) (24),对羟基苯甲酸(25),甲基苯甲酸(26),间甲基苯甲酸(27), 3-吲哚甲酸(28), 1-(O-5,9,13-trimethyltetradecanoyl)-glycerol (29), 18-羟基硬脂酸(30), 1-O-cis-9-octadecenylglycerol (31), batyl alcohol (32), 7(Z),10(Z)-Hexadecadienoic acid (33),十八烷酸(34),β-D-吡喃岩藻糖乙二醇苷(35)。其中化合物16 ~ 20和24为新化合物,化合物23, 29, 35为新天然产物。
采用MTT法测定了其中20个化合物的细胞毒活性,结果表明,化合物7对慢性髓原白血病细胞(K562)和人肝癌细胞(SMMC-7721)的增殖显示了较强的生长抑制活性;化合物16对人白血病细胞(K562)和人胃癌细胞(SGC-7902)有较强的细胞毒活性;化合物17对人白血病细胞(K562)有较强的细胞毒活性。采用滤纸片扩散法测定了所有化合物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌(MRSA),白色念珠菌的生长抑制活性。只有化合物30对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌有较弱的抑制活性。还采用滤纸片扩散法测定了其中10个化合物对农业病原菌:辣椒疫霉(Phytophthora capsici)、瓜果腐霉(Pythium aphanidermatum)、钟器腐霉(Pythium vexans)和尖孢镰刀菌(Fusarium oxysporum f.sp. cubense)的生长抑制活性,但是没有发现活性。
The South China Sea is a rich resource of acquiring secondary metabolites of unique structure with various bioactivities such as anti–tubercular, anti-tumor, anti-virus,antibiosis, ,anti-inflammatory, anti-allergy, treatments for neurological disorders and osteoporosis, and immunomodulation.
According to the methodology of chemical ecology combining with modern technology of marine natural products, in this paper, study of the chemical constituents of the sponge Haliclona cymaeformis and Topsentia sp. which was collected from the South China Sea, was carried out. The compounds were isolated and purified by column chromatography on silica gel, reversed-phase silica gel (ODS) and Sephadex LH-20, and their structures were elucidated on the basis of physicochemical and sp.tral analysis. As a result, Fifteen compounds were isolated from the ethanol extract of H. cymaeformis, and their structures were identified as 9-(4’-carbonypentan-2’(R)-yl)purine-6-hydroxy(1), 7- (4’-carbonypentan-2’-yl)purine -2-hydroxy(2), 7-(5’-carbonylpentan-3’-yl)purine-2-hydroxy (3), 7- (4’- carbonylpentan-2’-yl)purine-2-hydroxy (4),24-methylene-cholesta-3β-ol (5), 5α,8β-epidioxy-cholesta-6-en-3-ol (6), cholesta-7-en-3β,5α,6β,9α-tetraol (7), cholesterol (8), 1H-indole-3-carboxylic acid (9), uracil (10), thymine (11), uridine (12), thymidine (13), 2'-deoxyuridine (14), and 2'-deoxythymidine (15), resp.tively. Compounds 1– 4 were new purine alkaloids, Compounds 5– 15 were obtained from the sponge H. cymaeformis for the first time. Moreover, twenty-two compounds were isolated from the ethanol extract of Topsentia sp., and twenty of their structures were identified as Topsentiasterol (F-J) (16-20) (22E)-24-Isopropyl-22-dehydrocholesterol (21), cholesterol (22), Hydroxy-(4-hydroxyphenyl)-acetic acid ethyl ester (23), diethyl 2,2'-(4,4'-oxybis(4,1-phenylene)) bis(2-hydroxyacetate) (24),4-Hydroxybenzoic acid (25), 4-Methylbenzoic acid (26), 2-Methylbenzoic acid (27), 1H-indole-3-carboxylic acid (28), 1-(O-5,9,13-trimethyltetradecanoyl)-glycerol (29), Octadecanoic acid (30), 1-O-cis-9-octadecenylglycerol (31), batyl alcohol (32), 7(Z),10(Z)-Hexadecadienoic acid (33), stearic acid (34),β-D-Fucoside-O-ethylene glycol (35)。Compounds 16– 20 and 24 were new compounds, compounds 23, 29, 35 were new natural products.
The cytotoxic activities was tested by MTT assay, Compounds 7 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) and human hepatoma (SMMC-7721) cell lines. Compounds 16 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) and human gastric carcinoma (SGC-7901) cell lines. Compounds 17 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) cell lines. The antimicrobial activities against Staphylococcus aureus, and Methicillin-resitant Staphylococcus aureus (MRSA), were measured using paper disco diffusion method. Consequently, only compound 30 showed weak inhibitory activity against both S. aureus and MRSA. The antimicrobial activities against Phytophthora capsiciPythium aphanidermatum, Pythium vexans,and Fusarium oxysporum f.sp. cubense were also tested, unfurturaly, no activity was found
引文
[1] Copp B R, Pearce A N. Natural product growth inhibitors of Mycobacterium tuberculosis[J]. Nat Prod Rep. 2007, 24(2): 278-297.
[2] Faulkner D J. Marine natural products[J]. Nat Prod Rep. 2002, 19(1): 1-49.
[3] Newman D J, Cragg G M. Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials.[J]. J. Nat. Prod. 2004, 67(8): 1216-1238.
[4]黄孝春,郭跃伟.海绵药物的研究进展:化学和生物活性[J].中国天然药物. 2005(01).
[5] Newman D J, Cragg G M. Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials[J]. J Nat Prod. , 67(8): 1216-1238.
[6] Schwartsmann G, Da Rocha A B, Mattei J, et.al. Marine-derived anticancer agents in clinical trials[J]. Expert Opin Inv Drug. 2003, 12(8): 1367-1383.
[7] Zhang W, Guo Y, Gu Y. Secondary metabolites from the South China Sea invertebrates: chemistry and biological activity.[J]. Curr. Med. Chem. 2006, 13(17): 2041-2090.
[8]黄宗国.中国海洋生物种类与分布[M].北京:海洋出版社.
[9]薛多清,王俊杰,刘海利,等.海洋天然产物研究进展[J]. 2009: 7, 150-160.
[10] Mao S, Manzo E, Guo Y, et.al. New diastereomeric bis-sesquiterpenes from Hainan marine sponges Axinyssa variabilis and Lipastrotethya ana.[J]. Tetrahedron. 2007, 63(45): 11108-11113.
[11] Xue D, Mollo E, Cimino G, et.al. Lingshuine, an Unexpected Passerini Product from the Hainan Sponge Axinyssa variabilis.[J]. Helv. Chim. Acta. 2009, 92(7): 1428-1433.
[12] Lan W, Li H. New sesterterpenoids from the marine sponge Phyllospongia papyracea.[J]. Helv. Chim. Acta. 2007, 90(6): 1218-1222.
[13] Lin H, Wang Z, Chen W, et.al. Purification of triterpenes from Stelletta tenuis Lindgren for use as antitumor agent.[P]. CN, Application: CN2007-10042653. 2008-01-30[2008-01-30].
[14] Lin H, Wang Z, Wu J, et.al. Stellettins L and M, Cytotoxic Isomalabaricane-Type Triterpenes, and Sterols from the Marine Sponge Stelletta tenuis.[J]. J. Nat. Prod. 2007, 70(7): 1114-1117.
[15] Li J, Xu B, Cui J, et.al. Globostelletins A-I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata.[J]. Bioorg. Med. Chem. 2010, 18(13): 4639-4647.
[16] Tang S, Deng Z, Proksch P, et.al. Jaspolides G and H, unique bisisomalabaricanes from the Chinese marine sponge Jaspis sp.[J]. Tetrahedron Lett. 2007, 48(31): 5443-5447.
[17] Tang S, Pei Y, Fu H, et.al. Jaspolides A-F, six new isomalabricane-type terpenoids from the sponge Jaspis sp.[J]. Chem. Pharm. Bull. 2006, 54(1): 4-8.
[18]刘永宏,王宾,刘大有,等.蜂海绵属Haliclona海绵化学成分及生物活性研究综述[J].热带海洋学报, : 28, 70-82.
[19] Schmitz F J, Hollenbeak K H, Campbell D C. Marine natural products: halitoxin, toxic complex of several marine sponges of the genus Haliclona.[J]. J. Org. Chem. 1978, 43(20): 3916-3922.
[20] Fusetani N, Yasumuro K, Matsunaga S, et.al. Haliclamines A and B, cytotoxic macrocyclic alkaloids from a sponge of the genus Haliclona.[J]. Tetrahedron Lett. 1989, 30(49): 6891-6894.
[21] Volk C A, K?ck M. Viscosamine: The First Naturally Occurring Trimeric 3-Alkyl Pyridinium Alkaloid[J]. 2003, 5(20): 3567-3569.
[22] Schmidt G, Timm C, Koeck M. New haliclamines E and F from the Arctic sponge Haliclona viscosa.[J]. Org. Biomol. Chem. 2009, 7(15): 3061-3064.
[23] Teruya T, Kobayashi K, Suenaga K, et.al. Cyclohaliclonamines A-E: Dimeric, trimeric, tetrameric, pentameric, and hexameric 3-alkyl pyridinium alkaloids from a marine sponge Haliclona sp.[J]. J. Nat. Prod. 2006, 69(1): 135-137.
[24] Volk C A, Koeck M. Viscosaline: new 3-alkyl pyridinium alkaloid from the Arctic sponge Haliclona viscosa.[J]. Org. Biomol. Chem. 2004, 2(13): 1827-1830.
[25] Jaspars M, Horton P A, Madrid L H, et.al. The cyclorenierins, sesquiterpenoid quinols from the sponge Haliclona sp. collected in Vanuatu.[J]. J. Nat. Prod. 1995, 58(4): 609-612.
[26] Blackburn C L, Hopmann C, Sakowicz R, et.al. Adociasulfates 1-6, inhibitors of kinesin motor proteins from the sponge Haliclona (aka Adocia) sp.[J]. J. Org. Chem. 1999, 64(15): 5565-5570.
[27] Blackburn C L, Faulkner D J. Adociasulfate 10, a new merohexaprenoid sulfate from the sponge Haliclona (aka Adocia) sp.[J]. Tetrahedron. 2000, 56(43): 8429-8432.
[28] Crews P, Harrison B. New triterpene-ketides (merotriterpenes), haliclotriol A and B, from an Indo-Pacific Haliclona sponge.[J]. Tetrahedron. 2000, 56(46): 9039-9046.
[29] Fu X, Ferreira M L G, Schmitz F J, et.al. Tamosterone sulfates: a C-14 epimeric pair of polyhydroxylated sterols from a new oceanapiid sponge genus.[J]. J. Org. Chem. 1999, 64(18): 6706-6709.
[30] De Jesus R P, Faulkner D J. Chlorinated acetylenes from the San Diego sponge Haliclona lunisimilis.[J]. J. Nat. Prod. 2003, 66(5): 671-674.
[31] Shin J, Seo Y, Cho K W, et.al. Osirisynes A-F, highly oxygenated polyacetylenes from the sponge Haliclona osiris. [Erratum to document cited in CA129:200709].[J]. Tetrahedron. 1998, 54(49): 14636.
[32] Aoki S, Matsui K, Tanaka K, et.al. Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp.[J]. Tetrahedron. 2000, 56(51): 9945-9948.
[33] Bartik K, Braekman J C, Daloze D, et.al. Topsentins, new toxic bis-indole alkaloids from the marine sponge Topsentia genitrix.[J]. Can. J. Chem. 1987, 65(9): 2118-2121.
[34] Ciminiello P, Fattorusso E, Magno S, et.al. Three new D-ring unsaturated sterols from the Mediterranean sponge Topsentia aurantiaca: structure determination and complete nuclear magnetic resonance assignment.[J]. Steroids. 1992, 57(2): 62-66.
[35] Mckee T C, Cardellina J H I, Tischler M, et.al. Ibisterol sulfate, a novel HIV-inhibitory sulfated sterol from the deep water sponge Topsentia sp.[J]. Tetrahedron Lett. 1993, 34(3): 389-392.
[36] Gunasekera S P, Sennett S H, Kelly-Borges M, et.al. Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites.[J]. J. Nat. Prod. 1994, 57(12): 1751-1754.
[37] Slate D L, Lee R H, Rodriguez J, et.al. The marine natural product, halistanol trisulfate, inhibits pp60v-src protein tyrosine kinase activity.[J]. Biochem. Biophys. Res. Commun. 1994, 203(1): 260-264.
[38] Tsukamoto S, Kato H, Hirota H, et.al. Antifouling terpenes and steroids against barnacle larvae from marine sponges.[J]. Biofouling. 1997, 11(4): 283-291.
[39] Ishibashi M, Yamagishi E, Kobayashi J. Topsentinols A-J, new sterols with highly branched side chains from marine sponge Topsentia sp.[J]. Chem. Pharm. Bull. 1997, 45(9): 1435-1438.
[40] Calderon G J, Castellanos L, Duque C, et.al. Ophirasterol, a new C31 sterol from the marine sponge Topsentia ophiraphidites.[J]. Steroids. 2004, 69(2): 93-100.
[41] Luo X, Li F, Shinde P B, et.al. 26,27-Cyclosterols and Other Polyoxygenated Sterols from a Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2006, 69(12): 1760-1768.
[42] Kossuga M H, De Lira S P, Nascimento A M, et.al. Isolation and biological activities of secondary metabolites from the sponges Monanchora arbuscula, Aplysina sp., Petromica ciocalyptoides and Topsentia ophiraphidites, from the ascidian Didemnum ligulum and from the octocoral Carijoa riisei.[J]. Quim. Nova. 2007, 30(5): 1194-1202.
[43] Guzii A G, Makarieva T N, Denisenko V A, et.al. Topsentiasterol sulfates with novel iodinated and chlorinated side chains from the marine sponge Topsentia sp.[J]. Tetrahedron Lett. 2008, 49(50): 7191-7193.
[44] Di Girolamo J A, Li X, Jacob M R, et.al. Reversal of Fluconazole Resistance by Sulfated Sterols from the Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2009, 72(8): 1524-1528.
[45] Dai J, Sorribas A, Yoshida W Y, et.al. Topsentinols, 24-Isopropyl Steroids from the Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2010, 73(9): 1597-1600.
[46] Braekman J C, Daloze D, Stoller C. Synthesis of topsentin-A, a bisindole alkaloid of the marine sponge Topsentia genitrix.[J]. Bull. Soc. Chim. Belg. 1987, 96(10): 809-812.
[47] Braekman J C, Daloze D, Moussiaux B, et.al. Sponge secondary metabolites: new results.[J]. Pure Appl. Chem. 1989, 61(3): 509-512.
[48] Gunasekera S P, Cross S S. Isolation of topsentin analogs from Topsentia and their use as antitumor and antiviral agents.[P]. EP, Application: EP1988-306402. 1989-02-22[1989-02-22].
[49] Yang C, Huang H, Jiang B. Progress in studies of novel marine bis(indole) alkaloids.[J]. Curr. Org. Chem. 2004, 8(17): 1691-1720.
[50] Alvi K A, Tenenbaum L, Crews P. Anthelmintic polyfunctional nitrogen-containing terpenoids from marine sponges.[J]. J. Nat. Prod. 1991, 54(1): 71-78.
[51] Luo X, Li F, Hong J, et.al. Cytotoxic oxylipins from a marine sponge Topsentia sp.[J]. J. Nat. Prod. 2006, 69(4): 567-571.
[52] Carballeira N M, Negron V, Reyes E D. Novel naturally occurring alpha -methoxy acids from the phospholipids of caribbean sponges.[J]. Tetrahedron. 1992, 48(6): 1053-1058.
[53] Wattanadilok R, Sawangwong P, Rodrigues C, et.al. Antifungal activity evaluation of the constituents of Haliclona baeri and Haliclona cymaeformis, collected from the Gulf of Thailand.[J]. Mar Drugs. 2007, 5(2): 40-51.
[54] Bugni T S, Concepci G P, Mangalindan G C, et.al. p-Sulfooxyphenylpyruvic acid from the red macro alga Ceratodictyon spongiosum and its sponge symbiont Haliclona cymaeformis[J]. Phytochemistry. 2002, 60(4): 361-363.
[55] Akiyama T, Ueoka R, Van Soest R W M, et.al. Ceratodictyols, 1-Glyceryl Ethers from the Red Alga?Sponge Association Ceratodictyon spongiosum/Haliclona cymaeformis[J]. 2009, 72(8): 1552-1554.
[56] Al Y M, Bashir A K, Blunden G, et.al. 6-Methylcryptoacetalide, 6-methyl-epicryptoacetalide and 6-methylcryptotanshinone from Salvia aegyptiaca.[J]. Phytochemistry. 2002, 61(4): 361-365.
[57] T M. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays[J]. J Immunol Methods. 1983, 65(1-2): 55-63.
[58] Jones A J, Grant D M, Winkley M W, et.al. Carbon-13 magnetic resonance. XVII. Pyrimidine and purine nucleosides[J]. 1970, 92(13): 4079-4087.
[59] Gandelman M, Jacobsen E N. Highly enantioselective catalytic conjugate addition of N-heterocycles to alpha ,beta -unsaturated ketones and imides.[J]. Angew. Chem., Int. Ed. 2005, 44(16): 2393-2397.
[60]李瑞声,温文坚,汪波.中国南海软珊瑚Nephthea Bayer的化学成分研究——19-羟基-24-亚甲基多羟基甾醇的分离鉴定[J].中国海洋药物. 1996(04): 5-12.
[61] Ioannou E, Abdel-Razik A F, Zervou M, et.al. 5alpha,8alpha-Epidioxysterols from the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum: isolation and evaluation of their antiproliferative activity.[J]. Steroids. 2009, 74(1): 73-80.
[62] Xu L, Korade Z, Porter N A. Oxysterols from Free Radical Chain Oxidation of 7-Dehydrocholesterol: Product and Mechanistic Studies[J]. J Am Chem Soc. 2010, 132(7): 2222-2232.
[63]葛洁虹,高程海,王萍,等.南海二叉黑角珊瑚化学成分研究[J].中药材. 2010(09): 1403-1405.
[64] Bano S, Ali M S, Ahmad V U. Marine Natural Products; VI. A Halogenated Chamigrene Epoxide from the Red Alga Laurencia pinnatifida.[J]. Planta Med. 1987, 53(5): 508.
[65]张淑瑜,汤海峰,易杨华,等.棕环海参化学成分的研究[J].中国海洋药物. 2006(06): 7-13.
[66]张淑瑜,汤海峰,易杨华,等.棕环海参化学成分的研究[J].中国海洋药物. 2006(06): 7-13.
[67]徐银峰,王斌,苏传玲,等.蜈蚣藻的化学成分(英文)[J].中国天然药物. 2010(05): 326-329.
[68]黄胜阳,石建功,杨永春,等.长苞凹舌兰化学成分研究[J].药学学报. 2002(03): 199-203.
[69]史雪凤,唐旭利,李国强,等.中国南海高领类尖柳珊瑚Muriceides collaris化学成分研究[J].中国海洋药物. 2009(02): 18-21.
[70]张立新,范晓,韩丽君.罗氏海盘车(Asterias rollestoni)中几种化合物的提取分离和结构鉴定[J].天然产物研究与开发. 2005(01): 35-37.
[71] Elkin G J, Elkin H D, Aljendro M M. Halistanol triacetate, a derivative of a bioactive metabolite from Colombian marine sponge Topsentia ophiraphidites.[J]. Vitae. 2006, 13(2): 83-87.
[72] Calderon G J, Castellanos L, Duque C, et.al. Ophirasterol, a new C31 sterol from the marine sponge Topsentia ophiraphidites.[J]. Steroids. 2004, 69(2): 93-100.
[73] Zhang W, Shi M. Reduction of activated carbonyl groups by alkyl phosphines: formation of alpha -hydroxy esters and ketones.[J]. Chem. Commun. (Cambridge, U. K.). 2006(11): 1218-1220.
[74] Sivakumar S, Reddy M L P, Cowley A H,等. Synthesis and crystal structures of lanthanide 4-benzyloxy benzoates: Influence of electron-withdrawing and electron-donating groups on luminescent properties.[J]. Dalton Trans. 2010, 39(3): 776-786.
[75] Kobayashi K, Kondo Y. Transition-Metal-Free Carboxylation of Organozinc Reagents Using CO2 in DMF Solvent[J]. Org Lett. 2009, 11(9): 2035-2037.
[76] Fong C, Wells D, Krodkiewska I, et.al. Synthesis and Mesophases of Glycerate Surfactants.[J]. J. Phys. Chem. B. 2007, 111(6): 1384-1392.
[77] Halldorsson A, Thordarson P, Kristinsson B, et.al. Lipase-catalyzed kinetic resolution of 1-O-alkylglycerols by sequential transesterification.[J]. Tetrahedron: Asymmetry. 2004, 15(18): 2893-2899.
[78]姚仲青,郭青.海州常山叶的化学成分研究(Ⅰ)[J].中国实验方剂学杂志. 2010(06): 103-104.
[79]于德泉,杨俊山.分析化学手册(第七分册)[M].北京:化学工业出版社, 902.
[80] Morales J C, Reina J J, Diaz I, et.al. Experimental measurement of carbohydrate-aromatic stacking in water by using a dangling-ended DNA model system.[J]. Chem.--Eur. J. 2008, 14(26): 7828-7835.
[2] Faulkner D J. Marine natural products[J]. Nat Prod Rep. 2002, 19(1): 1-49.
[3] Newman D J, Cragg G M. Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials.[J]. J. Nat. Prod. 2004, 67(8): 1216-1238.
[4]黄孝春,郭跃伟.海绵药物的研究进展:化学和生物活性[J].中国天然药物. 2005(01).
[5] Newman D J, Cragg G M. Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials[J]. J Nat Prod. , 67(8): 1216-1238.
[6] Schwartsmann G, Da Rocha A B, Mattei J, et.al. Marine-derived anticancer agents in clinical trials[J]. Expert Opin Inv Drug. 2003, 12(8): 1367-1383.
[7] Zhang W, Guo Y, Gu Y. Secondary metabolites from the South China Sea invertebrates: chemistry and biological activity.[J]. Curr. Med. Chem. 2006, 13(17): 2041-2090.
[8]黄宗国.中国海洋生物种类与分布[M].北京:海洋出版社.
[9]薛多清,王俊杰,刘海利,等.海洋天然产物研究进展[J]. 2009: 7, 150-160.
[10] Mao S, Manzo E, Guo Y, et.al. New diastereomeric bis-sesquiterpenes from Hainan marine sponges Axinyssa variabilis and Lipastrotethya ana.[J]. Tetrahedron. 2007, 63(45): 11108-11113.
[11] Xue D, Mollo E, Cimino G, et.al. Lingshuine, an Unexpected Passerini Product from the Hainan Sponge Axinyssa variabilis.[J]. Helv. Chim. Acta. 2009, 92(7): 1428-1433.
[12] Lan W, Li H. New sesterterpenoids from the marine sponge Phyllospongia papyracea.[J]. Helv. Chim. Acta. 2007, 90(6): 1218-1222.
[13] Lin H, Wang Z, Chen W, et.al. Purification of triterpenes from Stelletta tenuis Lindgren for use as antitumor agent.[P]. CN, Application: CN2007-10042653. 2008-01-30[2008-01-30].
[14] Lin H, Wang Z, Wu J, et.al. Stellettins L and M, Cytotoxic Isomalabaricane-Type Triterpenes, and Sterols from the Marine Sponge Stelletta tenuis.[J]. J. Nat. Prod. 2007, 70(7): 1114-1117.
[15] Li J, Xu B, Cui J, et.al. Globostelletins A-I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata.[J]. Bioorg. Med. Chem. 2010, 18(13): 4639-4647.
[16] Tang S, Deng Z, Proksch P, et.al. Jaspolides G and H, unique bisisomalabaricanes from the Chinese marine sponge Jaspis sp.[J]. Tetrahedron Lett. 2007, 48(31): 5443-5447.
[17] Tang S, Pei Y, Fu H, et.al. Jaspolides A-F, six new isomalabricane-type terpenoids from the sponge Jaspis sp.[J]. Chem. Pharm. Bull. 2006, 54(1): 4-8.
[18]刘永宏,王宾,刘大有,等.蜂海绵属Haliclona海绵化学成分及生物活性研究综述[J].热带海洋学报, : 28, 70-82.
[19] Schmitz F J, Hollenbeak K H, Campbell D C. Marine natural products: halitoxin, toxic complex of several marine sponges of the genus Haliclona.[J]. J. Org. Chem. 1978, 43(20): 3916-3922.
[20] Fusetani N, Yasumuro K, Matsunaga S, et.al. Haliclamines A and B, cytotoxic macrocyclic alkaloids from a sponge of the genus Haliclona.[J]. Tetrahedron Lett. 1989, 30(49): 6891-6894.
[21] Volk C A, K?ck M. Viscosamine: The First Naturally Occurring Trimeric 3-Alkyl Pyridinium Alkaloid[J]. 2003, 5(20): 3567-3569.
[22] Schmidt G, Timm C, Koeck M. New haliclamines E and F from the Arctic sponge Haliclona viscosa.[J]. Org. Biomol. Chem. 2009, 7(15): 3061-3064.
[23] Teruya T, Kobayashi K, Suenaga K, et.al. Cyclohaliclonamines A-E: Dimeric, trimeric, tetrameric, pentameric, and hexameric 3-alkyl pyridinium alkaloids from a marine sponge Haliclona sp.[J]. J. Nat. Prod. 2006, 69(1): 135-137.
[24] Volk C A, Koeck M. Viscosaline: new 3-alkyl pyridinium alkaloid from the Arctic sponge Haliclona viscosa.[J]. Org. Biomol. Chem. 2004, 2(13): 1827-1830.
[25] Jaspars M, Horton P A, Madrid L H, et.al. The cyclorenierins, sesquiterpenoid quinols from the sponge Haliclona sp. collected in Vanuatu.[J]. J. Nat. Prod. 1995, 58(4): 609-612.
[26] Blackburn C L, Hopmann C, Sakowicz R, et.al. Adociasulfates 1-6, inhibitors of kinesin motor proteins from the sponge Haliclona (aka Adocia) sp.[J]. J. Org. Chem. 1999, 64(15): 5565-5570.
[27] Blackburn C L, Faulkner D J. Adociasulfate 10, a new merohexaprenoid sulfate from the sponge Haliclona (aka Adocia) sp.[J]. Tetrahedron. 2000, 56(43): 8429-8432.
[28] Crews P, Harrison B. New triterpene-ketides (merotriterpenes), haliclotriol A and B, from an Indo-Pacific Haliclona sponge.[J]. Tetrahedron. 2000, 56(46): 9039-9046.
[29] Fu X, Ferreira M L G, Schmitz F J, et.al. Tamosterone sulfates: a C-14 epimeric pair of polyhydroxylated sterols from a new oceanapiid sponge genus.[J]. J. Org. Chem. 1999, 64(18): 6706-6709.
[30] De Jesus R P, Faulkner D J. Chlorinated acetylenes from the San Diego sponge Haliclona lunisimilis.[J]. J. Nat. Prod. 2003, 66(5): 671-674.
[31] Shin J, Seo Y, Cho K W, et.al. Osirisynes A-F, highly oxygenated polyacetylenes from the sponge Haliclona osiris. [Erratum to document cited in CA129:200709].[J]. Tetrahedron. 1998, 54(49): 14636.
[32] Aoki S, Matsui K, Tanaka K, et.al. Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp.[J]. Tetrahedron. 2000, 56(51): 9945-9948.
[33] Bartik K, Braekman J C, Daloze D, et.al. Topsentins, new toxic bis-indole alkaloids from the marine sponge Topsentia genitrix.[J]. Can. J. Chem. 1987, 65(9): 2118-2121.
[34] Ciminiello P, Fattorusso E, Magno S, et.al. Three new D-ring unsaturated sterols from the Mediterranean sponge Topsentia aurantiaca: structure determination and complete nuclear magnetic resonance assignment.[J]. Steroids. 1992, 57(2): 62-66.
[35] Mckee T C, Cardellina J H I, Tischler M, et.al. Ibisterol sulfate, a novel HIV-inhibitory sulfated sterol from the deep water sponge Topsentia sp.[J]. Tetrahedron Lett. 1993, 34(3): 389-392.
[36] Gunasekera S P, Sennett S H, Kelly-Borges M, et.al. Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites.[J]. J. Nat. Prod. 1994, 57(12): 1751-1754.
[37] Slate D L, Lee R H, Rodriguez J, et.al. The marine natural product, halistanol trisulfate, inhibits pp60v-src protein tyrosine kinase activity.[J]. Biochem. Biophys. Res. Commun. 1994, 203(1): 260-264.
[38] Tsukamoto S, Kato H, Hirota H, et.al. Antifouling terpenes and steroids against barnacle larvae from marine sponges.[J]. Biofouling. 1997, 11(4): 283-291.
[39] Ishibashi M, Yamagishi E, Kobayashi J. Topsentinols A-J, new sterols with highly branched side chains from marine sponge Topsentia sp.[J]. Chem. Pharm. Bull. 1997, 45(9): 1435-1438.
[40] Calderon G J, Castellanos L, Duque C, et.al. Ophirasterol, a new C31 sterol from the marine sponge Topsentia ophiraphidites.[J]. Steroids. 2004, 69(2): 93-100.
[41] Luo X, Li F, Shinde P B, et.al. 26,27-Cyclosterols and Other Polyoxygenated Sterols from a Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2006, 69(12): 1760-1768.
[42] Kossuga M H, De Lira S P, Nascimento A M, et.al. Isolation and biological activities of secondary metabolites from the sponges Monanchora arbuscula, Aplysina sp., Petromica ciocalyptoides and Topsentia ophiraphidites, from the ascidian Didemnum ligulum and from the octocoral Carijoa riisei.[J]. Quim. Nova. 2007, 30(5): 1194-1202.
[43] Guzii A G, Makarieva T N, Denisenko V A, et.al. Topsentiasterol sulfates with novel iodinated and chlorinated side chains from the marine sponge Topsentia sp.[J]. Tetrahedron Lett. 2008, 49(50): 7191-7193.
[44] Di Girolamo J A, Li X, Jacob M R, et.al. Reversal of Fluconazole Resistance by Sulfated Sterols from the Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2009, 72(8): 1524-1528.
[45] Dai J, Sorribas A, Yoshida W Y, et.al. Topsentinols, 24-Isopropyl Steroids from the Marine Sponge Topsentia sp.[J]. J. Nat. Prod. 2010, 73(9): 1597-1600.
[46] Braekman J C, Daloze D, Stoller C. Synthesis of topsentin-A, a bisindole alkaloid of the marine sponge Topsentia genitrix.[J]. Bull. Soc. Chim. Belg. 1987, 96(10): 809-812.
[47] Braekman J C, Daloze D, Moussiaux B, et.al. Sponge secondary metabolites: new results.[J]. Pure Appl. Chem. 1989, 61(3): 509-512.
[48] Gunasekera S P, Cross S S. Isolation of topsentin analogs from Topsentia and their use as antitumor and antiviral agents.[P]. EP, Application: EP1988-306402. 1989-02-22[1989-02-22].
[49] Yang C, Huang H, Jiang B. Progress in studies of novel marine bis(indole) alkaloids.[J]. Curr. Org. Chem. 2004, 8(17): 1691-1720.
[50] Alvi K A, Tenenbaum L, Crews P. Anthelmintic polyfunctional nitrogen-containing terpenoids from marine sponges.[J]. J. Nat. Prod. 1991, 54(1): 71-78.
[51] Luo X, Li F, Hong J, et.al. Cytotoxic oxylipins from a marine sponge Topsentia sp.[J]. J. Nat. Prod. 2006, 69(4): 567-571.
[52] Carballeira N M, Negron V, Reyes E D. Novel naturally occurring alpha -methoxy acids from the phospholipids of caribbean sponges.[J]. Tetrahedron. 1992, 48(6): 1053-1058.
[53] Wattanadilok R, Sawangwong P, Rodrigues C, et.al. Antifungal activity evaluation of the constituents of Haliclona baeri and Haliclona cymaeformis, collected from the Gulf of Thailand.[J]. Mar Drugs. 2007, 5(2): 40-51.
[54] Bugni T S, Concepci G P, Mangalindan G C, et.al. p-Sulfooxyphenylpyruvic acid from the red macro alga Ceratodictyon spongiosum and its sponge symbiont Haliclona cymaeformis[J]. Phytochemistry. 2002, 60(4): 361-363.
[55] Akiyama T, Ueoka R, Van Soest R W M, et.al. Ceratodictyols, 1-Glyceryl Ethers from the Red Alga?Sponge Association Ceratodictyon spongiosum/Haliclona cymaeformis[J]. 2009, 72(8): 1552-1554.
[56] Al Y M, Bashir A K, Blunden G, et.al. 6-Methylcryptoacetalide, 6-methyl-epicryptoacetalide and 6-methylcryptotanshinone from Salvia aegyptiaca.[J]. Phytochemistry. 2002, 61(4): 361-365.
[57] T M. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays[J]. J Immunol Methods. 1983, 65(1-2): 55-63.
[58] Jones A J, Grant D M, Winkley M W, et.al. Carbon-13 magnetic resonance. XVII. Pyrimidine and purine nucleosides[J]. 1970, 92(13): 4079-4087.
[59] Gandelman M, Jacobsen E N. Highly enantioselective catalytic conjugate addition of N-heterocycles to alpha ,beta -unsaturated ketones and imides.[J]. Angew. Chem., Int. Ed. 2005, 44(16): 2393-2397.
[60]李瑞声,温文坚,汪波.中国南海软珊瑚Nephthea Bayer的化学成分研究——19-羟基-24-亚甲基多羟基甾醇的分离鉴定[J].中国海洋药物. 1996(04): 5-12.
[61] Ioannou E, Abdel-Razik A F, Zervou M, et.al. 5alpha,8alpha-Epidioxysterols from the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum: isolation and evaluation of their antiproliferative activity.[J]. Steroids. 2009, 74(1): 73-80.
[62] Xu L, Korade Z, Porter N A. Oxysterols from Free Radical Chain Oxidation of 7-Dehydrocholesterol: Product and Mechanistic Studies[J]. J Am Chem Soc. 2010, 132(7): 2222-2232.
[63]葛洁虹,高程海,王萍,等.南海二叉黑角珊瑚化学成分研究[J].中药材. 2010(09): 1403-1405.
[64] Bano S, Ali M S, Ahmad V U. Marine Natural Products; VI. A Halogenated Chamigrene Epoxide from the Red Alga Laurencia pinnatifida.[J]. Planta Med. 1987, 53(5): 508.
[65]张淑瑜,汤海峰,易杨华,等.棕环海参化学成分的研究[J].中国海洋药物. 2006(06): 7-13.
[66]张淑瑜,汤海峰,易杨华,等.棕环海参化学成分的研究[J].中国海洋药物. 2006(06): 7-13.
[67]徐银峰,王斌,苏传玲,等.蜈蚣藻的化学成分(英文)[J].中国天然药物. 2010(05): 326-329.
[68]黄胜阳,石建功,杨永春,等.长苞凹舌兰化学成分研究[J].药学学报. 2002(03): 199-203.
[69]史雪凤,唐旭利,李国强,等.中国南海高领类尖柳珊瑚Muriceides collaris化学成分研究[J].中国海洋药物. 2009(02): 18-21.
[70]张立新,范晓,韩丽君.罗氏海盘车(Asterias rollestoni)中几种化合物的提取分离和结构鉴定[J].天然产物研究与开发. 2005(01): 35-37.
[71] Elkin G J, Elkin H D, Aljendro M M. Halistanol triacetate, a derivative of a bioactive metabolite from Colombian marine sponge Topsentia ophiraphidites.[J]. Vitae. 2006, 13(2): 83-87.
[72] Calderon G J, Castellanos L, Duque C, et.al. Ophirasterol, a new C31 sterol from the marine sponge Topsentia ophiraphidites.[J]. Steroids. 2004, 69(2): 93-100.
[73] Zhang W, Shi M. Reduction of activated carbonyl groups by alkyl phosphines: formation of alpha -hydroxy esters and ketones.[J]. Chem. Commun. (Cambridge, U. K.). 2006(11): 1218-1220.
[74] Sivakumar S, Reddy M L P, Cowley A H,等. Synthesis and crystal structures of lanthanide 4-benzyloxy benzoates: Influence of electron-withdrawing and electron-donating groups on luminescent properties.[J]. Dalton Trans. 2010, 39(3): 776-786.
[75] Kobayashi K, Kondo Y. Transition-Metal-Free Carboxylation of Organozinc Reagents Using CO2 in DMF Solvent[J]. Org Lett. 2009, 11(9): 2035-2037.
[76] Fong C, Wells D, Krodkiewska I, et.al. Synthesis and Mesophases of Glycerate Surfactants.[J]. J. Phys. Chem. B. 2007, 111(6): 1384-1392.
[77] Halldorsson A, Thordarson P, Kristinsson B, et.al. Lipase-catalyzed kinetic resolution of 1-O-alkylglycerols by sequential transesterification.[J]. Tetrahedron: Asymmetry. 2004, 15(18): 2893-2899.
[78]姚仲青,郭青.海州常山叶的化学成分研究(Ⅰ)[J].中国实验方剂学杂志. 2010(06): 103-104.
[79]于德泉,杨俊山.分析化学手册(第七分册)[M].北京:化学工业出版社, 902.
[80] Morales J C, Reina J J, Diaz I, et.al. Experimental measurement of carbohydrate-aromatic stacking in water by using a dangling-ended DNA model system.[J]. Chem.--Eur. J. 2008, 14(26): 7828-7835.