海绵共附生真菌Purpureocillium lilacinum的化学成分及T细胞调节活性研究  

Structure and T cell regulatory activity of metabolites from the sponge-associated fungi Purpureocillium lilacinum

作　　者：郭黎 周路雨 蔡黎娟 韩华[1] 张文 GUO Li;ZHOU Luyu;CAI Lijuan;HAN Hua;ZHANG Wen(School of Medicine,Tongji University,Shanghai 200092,China;Ningbo Institute of Marine Medicine,Peking University,Ningbo 315832,China)

机构地区：[1]同济大学医学院,上海200092 [2]北京大学宁波海洋药物研究院,浙江宁波315832

出　　处：《中国海洋药物》2024年第2期53-59,共7页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(82173735);上海市科委国际合作基金项目(21430711400)资助。

摘　　要：目的对海绵Hymeniacidon sp.共附生真菌Purpureocillium lilacinum的化学成分及T细胞调节活性进行研究。方法运用硅胶柱色谱、凝胶柱色谱及高压液相色谱等色谱技术对真菌乙酸乙酯粗提物进行分离纯化得到单体化合物,通过现代波谱(核磁共振,质谱)及光谱(旋光)的综合运用并结合文献对照对化合物结构进行鉴定,运用流式实验对化合物T细胞调节活性进行测试。结果共分离获得5个甾体化合物,鉴定为(24R)-豆甾-4-烯-6β-醇-3-酮(1)、(22E,24R)-麦角甾-7,22-二烯-3β,5α,9α-三醇-6-酮(2)、(22E,24R)-麦角甾-7,22-二烯-3β,5α-二醇-6-酮(3)、麦角甾-5,24-二烯-3β-醇-7,23-二酮(4)及(22E,24R)-麦角甾-5,8,22-三烯-3β-醇-7-酮(5)。体外活性筛选实验中,化合物2~5在2.5~20μmol/L时对刀豆蛋白A(ConA)诱导的T细胞增殖显示抑制活性,化合物5在10μmol/L时对CD3+T细胞的增殖显示显著抑制活性,所有受试化合物对CD4+/CD8+T细胞分化活性均无影响。结论化合物1~4为首次从P.lilacinum中分离获得。本文是对化合物1~5 T细胞调节活性的首次报道。Objective To investigate the structure and T cell regulatory activity of metabolites from the fungi Purpureocillium lilacinum associated with the sponge Hymeniacidon sp..Methods The ethyl acetate crude extract of the fungi was purified by silica gel and Sephadex LH-20 column chromatography and high pressure liquid chromatography.The structures of the compounds were identified by the modern spectroscopic methods(nuclear magnetic resonance,mass spectrometry and optical rotation)in combination with the data reported in literature.The T cell regulatory activity of the compounds was tested by flow assay.Results Five steroids were isolated from the fungi P.lilacinum and identified as(24R)-stigmast-4-en-6β-ol-3-one(1),(22E,24R)-ergosta-7,22-dien-3β,5α,9α-triol-6-one(2),(22E,24R)-ergosta-7,22-dien-3β,5α-diol-6-one(3),ergosta-5,24-dien-3β-ol-7,23-diketone(4),and(22E,24R)-ergosta-5,8,22-trien-3β-ol-7-one(5).In an in vitro bioscreening,compound 2-5 showed inhibitory activity at 2.5-20μmol/L on T cell proliferation induced by concanavalin A(ConA).In particular,compound 5 showed significant inhibitory activity on CD3~+T cell proliferation at 10μmol/L.The tested compounds showed no activity toward the CD4~+/CD8~+ratio.Conclusion Compounds 1-4 were reported for the first time from the fungi P.lilacinum.This is the first report on the T cell regulatory activity of these compounds.

关 键 词：海绵共附生真菌 甾体 T细胞调节活性 

分 类 号：R931.77[医药卫生—生药学]