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[摘要]
目的 探究深海来源细菌Ochrobactrum sp.OUCMDZ-2164中的细胞毒活性代谢产物。方法 利用硅胶柱色谱、凝胶柱色谱和高效液相色谱等手段对发酵产物进行分离纯化,运用紫外、红外、质谱、核磁共振及圆二色谱等方法鉴定化合物的结构,采用MTT和细胞计数试剂盒-8(CCK-8)法分别评价化合物对乳腺癌MCF-7细胞和肺癌A549细胞及慢性髓性白血病K562细胞的增殖抑制活性。结果 从细菌Ochrobactrum sp.OUCMDZ-2164的发酵产物中分离获得了4个化合物,分别鉴定为3-O-去甲基三烯霉醇(1)、flazin(2)、flazin-3-carboxylic acid(3)和胸腺嘧啶(4)。化合物1在10 μmol/L浓度下对MCF-7细胞的增殖抑制率为61.5%。结论 化合物1为新的安沙霉素类化合物,命名为三烯霉素J,其具有一定的乳腺癌细胞毒活性。
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[Abstract]
Objective To identify the cytotoxic natural products from the deep-sea derived Ochrobactrum sp. OUCMDZ-2164. Methods The isolations and purifications of compounds were performed by means of column chromatography over silica gel and Sephadex LH-20 as well as HPLC. Their structures were elucidated through the analysis of UV, IR, MS, NMR and ECD spectra. The cytotoxicities against MCF-7, A549 and K562 cells were evaluated by MTT and CCK-8 methods. Results From the fermentation broth of Ochrobactrum sp. OUCMDZ-2164, we isolated and identified four compounds (1-4). Compound 1 was identified as a new ansamycin and named trienomycin J, and the structures of 1-4 were identified as 3-O-demethyltrienomycinol, flazin, flazin-3-carboxylic acid and thymine, respectively. Compound 1 showed cytotoxic effect on the MCF-7 cells with 61.5% inhibition rate at 10 μmol/L. Conclusion Compound 1 was a new ansamycin named trienomycin J, with cytotoxic activity against human breast cancer cells (MCF-7).
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[基金项目]
国家自然科学基金资助项目(U1501221);国家自然科学基金资助项目(41876172);广西自然科学基金青年科学基金项目(2018JJB150106)