王翠红,汤华,张悦,等.珊瑚共附生毛壳属真菌中的麦角甾醇成分及肿瘤干细胞增殖抑制活性[J].中国海洋药物,2016,35(3):11-18.
珊瑚共附生毛壳属真菌中的麦角甾醇成分及肿瘤干细胞增殖抑制活性
Tumor stem cell proliferation inhibitory activity of ergosterols from coral-associated fungus Cheatomium sp.
投稿时间:2016-02-07  修订日期:2016-03-03
DOI:
中文关键词:  珊瑚共附生真菌  毛壳属  麦角甾醇  肿瘤干细胞
English Keywords:coral-associated  fungus, Cheatomium  sp., ergosterols, human  hepatoma stem  cell
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作者单位E-mail
王翠红 福建中医药大学 chw_89044@126.com 
汤华 第二军医大学  
张悦 第二军医大学  
庄春林 第二军医大学  
孙鹏 第二军医大学  
李铁军 第二军医大学  
张文* 福建中医药大学药学院药物化学教研室

第二军医大学药学院海洋药物研究中心/海洋生物医药研究所
安徽中医药大学药学院
安徽中医药大学药学院 
wenzhang1968@163.com 
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中文摘要:
      目的 研究软珊瑚来源的毛壳属真菌(Cheatomium sp.)中的活性成分。方法 采用多种分离手段对毛壳属真菌的乙酸乙酯提取物进行分离纯化,运用现代波谱技术并结合文献报道数据,鉴定化合物的结构;采用CCK-8方法对化合物的肝癌干细胞增殖抑制活性进行了体外测试。结果 分离得到13个已知的麦角甾醇类化合物,其结构分别鉴定为:麦角甾醇(1),(22E,24R)-麦角甾-6,22-二烯-5α,8α-过氧-3β-醇(2),(22E,24R)-麦角甾-5,8(14),22-三烯-3β,15α-二羟基-7-酮(3),(22E,24R)-麦角甾-5,8(14),22-三烯-3β,15β-二羟基-7-酮(4),(22E,24R)-麦角甾-5,8,22-三烯-3β-羟基-7-酮(5),(22E,24R)-麦角甾-7,22-二烯-3β,5α,6α,9α-四醇(6),(22E,24R)-麦角甾-7,22-二烯-5α,6α-环氧-3β-醇(7),麦角甾-7,22-三烯-6β-甲氧基-3β,5α-二醇(8),(22E,24R)-麦角甾-7,22-二烯-3β,5α-二醇-6-酮(9),麦角甾-7,9(11),22-三烯-3β,5α,6α-三醇(10),(22E,24R)-麦角甾-7,22-二烯-3β,5α,6α-三醇(11),(22E,24R)-麦角甾-7,22-二烯-3β,5a,9a-三醇-6-酮(12),(22E,24R)-麦角甾-8,22-二烯-5α,6α-环氧-3β,7α-二醇(13)。在体外活性测试中,化合物3、4、6、8、13对人肝癌Huh7干细胞增殖显示不同程度的抑制活性。结论 化合物5~13为首次从该属真菌中分离得到。本文是对麦角甾醇类化合物抑制肿瘤干细胞增殖活性的首次报道。
English Summary:
      Objective To investigate the bioactive chemical constituents of fungus Cheatomium sp. associated with soft coral Cladiella sp. Method Compounds were isolated and purified by means of various chromatographic techniques, including silica gel and Sephadex LH-20 chromatography, and RP-HPLC. The structures of the isolates were determined based on spectroscopic analysis and comparison with reported data. The in vitro human hepatoma stem cell proliferation inhibition activity was tested using CCK-8 approach. Results Thirteen known ergoteroids were isolated and identified as: ergosterol (1), (22E,24R)-ergost-6,22-dien-5α,8α-epidioxy-3β-ol (2), (22E,24R)-ergost-5,8(14),22-trien-3β,15α-diol-7-one (3), (22E,24R)-ergost-5,8(14),22-trien-3β,15β-diol-7-one (4), (22E,24R)-ergost-5,8,22-trien-3β-ol-7-one (5), (22E,24R)-ergost-7,22-dien-3β,5α,6α,9α-tetrol (6), ( 22E,24R)-ergost-7,22-dien-5α,6α-epoxy-3β-ol (7), ergost-7,22-dien-6β-methoxy-3β,5α-diol (8), (22E,24R)-ergost-7,22-dien-3β,5α-diol-6-one (9), ergost-7,9(11),22-trien-3β,5α,6α-triol (10), (22E,24R)-ergost-7,22-dien-3β,5α,6α-triol (11), (22E,24R)-ergost-7,22-dien-3β,5a,9a-triol-6-one(12), (22E,24R)-ergost-8,22-dien-5α,6α-epoxy-3β,7α-diol (13). In the bioassay in vitro, compounds 3, 4, 6, 8 and 13 exhibited different levels of growth inhibition activity against Huh7 stem cells. Conclusion Compounds 5 ~13 were reported for the first time from the fungus Cheatomium sp. This is the first report of sterols for their tumor stem cell proliferation inhibitory activity.
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