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   

  1. 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 Conga, Wang Lipingb, Fan Jiea, Sun Kunlaia,c, Zhu Weiminga   

  1. 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).

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、89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58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