疣孢菌FIM090395细胞毒活性次级代谢产物的研究

Secondary metabolites with cytotoxic activities produced by Verrucosispora sp. FIM090395

目的研究分离自海洋沉积物的疣孢菌FIM090395产生的次级代谢产物。方法采用HP-20大孔吸附树脂、正相硅胶、Sephadex LH-20葡聚糖凝胶和反相C18柱层析等方法,对菌株FIM090395次级代谢产物进行分离纯化。通过紫外光谱、质谱、核磁共振等波谱学方法对化合物进行结构鉴定。结果与结论分离得到化合物1和化合物2,结构解析确定它们分别与proximicin A和B同质,活性研究表明化合物1对肿瘤细胞株MDA-MB-231(乳腺癌细胞)、SW620(结肠癌细胞)、SMMC7721(肝癌细胞)和CNE-2(鼻咽癌细胞)具有一定的抑制作用,其IC50值分别为23.49、13.48、34.96和16.28μg/mL;化合物2对肿瘤细胞株K562(白血病细胞)具有一定的抑制作用,其IC50值为25.69μg/mL,对MDA-MB-231和CNE-2的抑制增殖作用较弱。

Objective To study the metabolites of Verrucosispora FIM090395 from marine sediments. Methods The metabolites from the culture filtrate of FIM090395 were purified by macroporous resin HP-20, silica gel, sephadex LH-20 and C18 reversed phase column chromatography. The structure of the compounds were determined by UV spectra, LC-MS,^ 1H and ^13C-NMR data analyses. Results and Conclusion Two compounds（1 and 2） were isolated from the culture filtrate, they were identified as proximicin A and B, respectively. Compound 1 showed in vitro growth inhibitory activity against the tumor cell lines MDA-MB-231, SW620, SMMC7721 and CNE-2 with ICso values of 23.49, 13.48, 34.96 and 16.28μg/mL, respectively.Therefore Compound 2 showed growth inhibitory activity against K562 cells with IC50 values of 25.69μg/mL, almost no activity against MDA-MB-231 and CNE-2 cells.