深海链霉菌Streptomyces malaysiensis OUCMDZ-2167来源的细胞毒性产物

doi:10.6023/cjoc201609021

有机化学 ›› 2017, Vol. 37 ›› Issue (3): 658-666.DOI: 10.6023/cjoc201609021 上一篇下一篇

研究论文

深海链霉菌Streptomyces malaysiensis OUCMDZ-2167来源的细胞毒性产物

王聪^a, 王立平^b, 范杰^a, 孙坤来^a,c, 朱伟明^a

a 中国海洋大学医药学院海洋药物教育部重点实验室青岛 266003;
b 贵州省中国科学院天然产物化学重点实验室贵州 550002;
c 浙江海洋大学食品与医药学院舟山 316022

收稿日期:2016-09-18 修回日期:2016-11-17 发布日期:2016-11-29
通讯作者: 朱伟明,E-mail:weimingzhu@ouc.edu.cn E-mail:weimingzhu@ouc.edu.cn
基金资助:
国家自然科学基金（Nos.81561148012，41376148）、国家自然科学基金-广东及国家自然科学基金-山东联合（Nos.U1501221，U1406402）资助项目.

Cytotoxic Compounds from the DeepSea Sediment-Derived Streptomyces malaysiensis OUCMDZ-2167

Wang Cong^a, Wang Liping^b, Fan Jie^a, Sun Kunlai^a,c, Zhu Weiming^a

a Key Laboratory of Marine Drugs, Ministry Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003;
b Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou 550002;
c School of Food Science and Pharmaceutics, Zhejiang Ocean University, Zhoushan 316022

Received:2016-09-18 Revised:2016-11-17 Published:2016-11-29
Contact: 10.6023/cjoc201609021 E-mail:weimingzhu@ouc.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 81561148012, 41376148), the National Natural Science Foundation of China-Guangdong and the National Natural Science Foundation of China-Shandong Province Joint Funds (Nos. U1501221, U1406402).

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摘要/Abstract

研究深海沉积物来源的链霉菌Streptomyces malaysiensis OUCMDZ-2167的活性天然产物.采用硅胶和凝胶柱色谱及高效液相色谱等手段，从链霉菌S.malaysiensis OUCMDZ-2167的发酵产物中分离纯化了1个新的呋喃衍生物1以及10个已知物2~11；采用质谱、紫外、红外、核磁共振和比旋光等方法将其结构分别鉴定为：4-羟甲基呋喃-2-甲酸甲酯（1）、呋喃-2，4-二甲酸二甲酯（2）、格尔德霉素（3）、17-O-去甲基格尔德霉素（4）、尼日利亚菌素（5）、尼日利亚菌素钠（6）、30-O-乙酰基尼日利亚菌素（7）、奥布菌素（8）、洋橄榄叶素（9）、surugapyrone A（10）和杀菌素A（11）.采用细胞计数试剂盒-8（CCK-8）和噻唑蓝（MTT）法分别评价了化合物对K562和MCF-7及A549肿瘤细胞株的细胞毒活性，结果表明：化合物3、5~9对A549的半数抑制浓度（IC₅₀）分别为2.56±0.30、0.96±0.03、0.96±0.04、0.81±0.05、7.11±0.90和4.09±0.70 μmol·L^-1，化合物5~9对K562的IC₅₀值分别1.46±0.11、1.08±0.03、0.48±0.10、4.68±0.19和9.60±0.50 μmol·L^-1，化合物5、8和9对MCF-7的IC₅₀值分别为0.29±0.15、4.05±0.50和4.81±0.70 μmol·L^-1；其中化合物5~8对K562和A549以及化合物5和8对MCF-7的细胞毒活性为首次报道.

关键词: 深海链霉菌, 马来西亚链霉菌, 活性天然产物, 肿瘤细胞毒活性

This paper is designed to study the bioactive natural products sourced from the deep-sea sediment-derived Strep-tomyces malaysiensis OUCMDZ-2167. By means of column chromatography on silica gel, sephadex LH-20 and semi-prepa-rative HPLC, a new furan derivative 1 and ten known compounds 2~11 were isolated and purified from the fermentation broth of S. malaysiensis OUCMDZ-2167. Their structures were respectively elucidated as methyl 4-(hydroxymethyl)furan-2-carboxylate (1), dimethyl furan-2,4-dicarboxylate (2), geldanamycin (3), 17-O-demethylgeldanamycin (4), nigericin (5), nigericin sodium salt (6), 30-O-acetylnigericin (7), abierixin (8), elaiophylin (9), surugapyrone A (10) and germicidin A (11), by analyzing the MS, UV, IR, NMR and specific rotations. The cytotoxicities against MCF-7, A549 and K562 were evaluated by thiazolyl blue tetrazolium bromide (MTT) and the cell counting kit-8 (CCK-8) methods. The results showed that compounds 3 and 5~9 exhib-ited the cytotoxicities against A549 cell with the half inhibitory concentrations (IC₅₀) of 2.56±0.30, 0.96±0.03, 0.96±0.04, 0.81±0.05, 7.11±0.90 and 4.09±0.70 μmol·L^-1, respectively. Compounds 5~9 displayed the cytotoxicities against K562 cells with the IC₅₀ values of 1.46±0.11, 1.08±0.03, 0.48±0.10, 4.68±0.19 and 9.60±0.50 μmol·L^-1, respectively. And compounds 5, 8 and 9 showed cytotoxicities against MCF-7 cell with the IC₅₀ values of 0.29±0.15, 4.05±0.50 and 4.81±0.70 μmol·L^-1, respectively. It is the first time to report the cytotoxicities of compounds 5~8 against K562 and A549 cell lines and against MCF-7 cell line.

Key words: deep-sea Streptomyces, Streptomyces malaysiensis, bioactive natural products, cytotoxicity

引用此文

王聪, 王立平, 范杰, 孙坤来, 朱伟明. 深海链霉菌Streptomyces malaysiensis OUCMDZ-2167来源的细胞毒性产物[J]. 有机化学, 2017, 37(3): 658-666.

Wang Cong, Wang Liping, Fan Jie, Sun Kunlai, Zhu Weiming. Cytotoxic Compounds from the DeepSea Sediment-Derived Streptomyces malaysiensis OUCMDZ-2167[J]. Chin. J. Org. Chem., 2017, 37(3): 658-666.

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深海链霉菌Streptomyces malaysiensis OUCMDZ-2167来源的细胞毒性产物

Cytotoxic Compounds from the DeepSea Sediment-Derived Streptomyces malaysiensis OUCMDZ-2167

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