链霉菌Streptomyces sp.FIM18-327次级代谢产物的研究  

Studies on the secondary metabolites of Streptomyces sp.FIM18-327

作　　者：陈丽[1] 谢立君[1] 周剑[1] 林如[1] 温耀明 邱观荣 江红[1] 江宏磊[1] Chen Li;Xie Lijun;Zhou Jian;Lin Ru;Wen Yaoming;Qiu Guanrong;Jiang Hong;Jiang Honglei(Fujian Laboratory of Screening for Novel Microbial Products,Fujian Institute of Microbiology,Fuzhou 350007;Fujian Kerui Pharmaceutical Co.,Ltd.,Fuzhou 350313)

机构地区：[1]福建省微生物研究所,福建省新药(微生物)筛选重点实验室,福州350007 [2]福建科瑞药业有限公司,福州350313

出　　处：《中国抗生素杂志》2025年第1期33-40,共8页Chinese Journal of Antibiotics

基　　金：中央引导地方科技发展专项(No.2021L3016);福建省社会发展引导性项目(No.2022Y0044);福建省公益类科研院所专项(No.2022R1005006);福州市级科技计划项目(No.2021-P-26)。

摘　　要：目的本文对链霉菌Streptomyces sp.FIM18-327发酵液中的次级代谢产物进行研究。方法采用浸提、萃取、硅胶柱层析及制备HPLC等方法分离纯化次级代谢产物,其结构经MS、NMR波谱数据分析并与文献对比来确定。结果从该菌株发酵液中分离纯化得到6个化合物,均为吲哚并咔唑类生物碱,其结构分别鉴定为7-ethyl-UCN-01(1)、RK-1409(2)、RK-286C(3)、星孢菌素(4)、7-methoxy-RK-286C(5)、K252c(6)。结论化合物1~6均是首次从该菌株中分离获得,其中化合物1是新的天然产物,活性结果表明化合物1~3对人源乳腺癌细胞MCF-7和胃癌细胞NCI-N87的抑制活性较好,其IC_(50)值为0.14~2.29μmol/L;同时也发现它们对激酶PKCθ也具有很强的抑制活性,其IC_(50)值为IC_(50)值为0.19~60.9 nmol/L。该研究结果对丰富吲哚并咔唑类生物碱的种类、发现候选抗肿瘤药物等具有指导意义。Objective To investigate the secondary metabolites from the fermentation broth of Streptomyces sp.FIM18-327.Methods Soaking,extraction,silica gel column chromatography and semi-preparative HPLC steps were adopted to separate and purify the secondary metabolites.Their chemical structures were identified by MS and NMR and compared with the data in the literatures.Results Six compounds were isolated and purified from the fermentation broth of the strain,all of which were indole-3-carbazole alkaloids,and they were identified as 7-ethyl-UCN-01(1),RK-1409(2),RK-286C(3),staurosporine(4),7-methoxy-RK-286C(5)and K252c(6),respectively.Conclusion Six compounds were isolated from the strain Streptomyces sp.FIM18-327 for the first time.Among them,compound 1 was a new natural product.The bioactive assay showed that compounds 1-3 had good inhibitory activities against human breast cancer MCF-7 cells and gastric cancer NCI-N87 cells with IC_(50) values of 0.14~2.29μmol/L.Three compounds were also found to have strong inhibitory activity against PKCθ,with IC_(50) values of 0.19~60.9 nmol/L.The results of this study had guiding significance for enriching the types of indole carbazole alkaloids and discovering candidate anti-tumor drugs.

关 键 词：星孢菌素 分离纯化 结构鉴定 抗肿瘤活性 

分 类 号：R978.1[医药卫生—药品]