链霉菌NOV-0827产生的抗肿瘤活性成分的分离纯化和结构鉴定  

Isolation, purifi cation and structural identifi cation of components with antitumor activity produced by Streptomyces strain NOV-0827

作　　者：常颖[1] 杨煌建[2] 周剑[2] 黄维[2] 黄楷[2] 张引[2] 孙菲[2] 郑卫[1,2] 

机构地区：[1]福建医科大学药学院,福州350004 [2]福建省微生物研究所,福州350007

出　　处：《中国抗生素杂志》2014年第11期808-812,818,共6页Chinese Journal of Antibiotics

基　　金：国家"十一五"重大专项"微生物药物技术创新与新药创制产学研联盟(No.2010ZX09401-403)"

摘　　要：目的分离、纯化和鉴定链霉菌NOV-0827发酵液中的抗肿瘤活性成分。方法采用大孔吸附柱层析、硅胶柱层析、凝胶柱层析等方法对该菌株的次级代谢产物进行分离纯化;根据理化性质和波谱学方法进行化学结构的鉴定;利用MTT法来检测化合物的抗肿瘤活性。结果从该菌株发酵液中共分离到3个化合物,NOV-0827-A、NOV-0827-B和NOV-0827-C,经波谱方法鉴定分别与文献中报道的氨基香豆素类(aminocoumarin)抗生素新生霉素,大环内酰胺类抗生素GT-32A和GT-32B同质。活性研究表明NOV-0827-B和NOV-0827-C均对结肠癌细胞SW620具有较强的增殖抑制活性,其IC50值分别1.107μmol/m L和5.358μmol/m L。结论首次从同一陆生链霉菌菌株的发酵液中分离得到新生霉素及其他两个具有抗肿瘤活性的大环内酰胺类物质。Objective To isolate,purify and identify the structures of components with antitumor activity produced by Streptomyces NOV-0827 from the fermentation broth.Methods The secondary metabolites were isolated and purified by macroporous resin column chromatography,silica gel chromatography,gel column chromatography,etc.; the chemical structures were identified by physicochemical properties and spectroscopic methods; to detect antitumor activity by MTT assay.Results Three compounds NOV-0827-A,NOV-0827-B and NOV-0827-C were isolated from the fermentation broth and were identified separatively as the same as novobiocin （1）,GT-32A（2）,and GT-32B （3） on the basis of spectral data analysis.Studies shows that both NOV-0827-B and NOV-0827-C have strong growth inhibitory activity of SW620 cell,with IC50 values：1.107μmol/mL and 5.358μmol/mL,respectively.Conclusion Studies shows that novobiocin and two macrocyclic lactam compounds with antitumor activity are isolated from the fermentation broth of the same strain of terrestrial Streptomyces.

关 键 词：链霉菌 新生霉素 大环内酰胺 分离纯化 结构鉴定 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]