【作者】 杨爱岗； 董姣姣； 林文翰； 田黎；

【Author】 YANG Ai-gang1,DONG Jiao-jiao2,3,LIN Wen-han2,TIAN Li2,3 (1,State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China ; 2,The First Institute of Oceannography SOA,Qingdao 266061,China ; Qingdao Universiy of Science & Technology,Qingdao 266042,China )

【机构】 北京大学天然药物及仿生药物国家重点实验室； 国家海洋局第一海洋研究所； 青岛科技大学；

【摘要】 目的研究深海放线菌Streptomyces nitrosporeus中代谢的吲哚咔唑类生物碱以及其抑制酪氨酸激酶的活性。方法采用各种色谱方法对菌株代谢的化学成分进行了分离纯化,通过理化性质和波谱数据鉴定了化合物的结构,采用BaF3-TK细胞筛选模型对部分生物碱的酪氨酸激酶抑制活性进行了筛选。结果放线菌样品中共分离得到9个吲哚咔唑类生物碱生物碱,结构鉴定为staurosporine(1),K252c(2),K252d(3),K252a(4),MLR-52(5),4-demethylamino-4-oxostaurosporine(6),7-oxo-staurosporin(7),holyrine A(8)和Streptocarbazoles B(9);化合物1,3和4有酪氨酸激酶抑制活性。结论首次从该菌属中分离得到吲哚咔唑类生物碱,BaF3-TK细胞筛选模型检测化合物1和3有较强酪氨酸激酶抑制活性。更多还原

【Abstract】 OBJECTIVE To study the indolocarbazole alkaloids and their tyrosine kinase inhibitory activities of marine-derived actinomyces Streptomyces nitrosporeus.METHODS The compounds were isolated by different chromatographic techniques,and their structures were elucidated by means of physicochemical properties and spectral data;TKI activities were tested by BaF3-TK Cell screening model.RESULTS Nine indolecarbazole alkaloids were isolated from the mycelium of Streptomyces nitrosporeu,their structures were identified as staurosporine(1),K252a(2),K252c(3),K252d(4),MLR-52(5),4-demethylamino- 4-oxostaurosporine(6),7-oxo-staurosporin(7),holyrine A(8) and Streptocarbazoles B(9);among them,compound 1,3 and 4 showed respectively potent or moderate inhibitory activities against tyrosine kinase.CONLUSION All the indolecarbazole alkaloids were isolated for the first time from the genus of Streptomyces nitrosporeus,compound 1,3 were identified as TK inhibitor with the BaF3-TK Cell screening model.更多还原