有机化学 ›› 2019, Vol. 39 ›› Issue (2): 507-514.DOI: 10.6023/cjoc201806045 上一篇    下一篇

研究论文

海绵放线菌Nocardiopsis dassonvillei OUCMDZ-4534的活性天然产物

刘海珊, 朱国良, 赵水鸽, 付鹏, 朱伟明   

  1. 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
  • 收稿日期:2018-06-29 修回日期:2018-08-08 发布日期:2018-09-05
  • 通讯作者: 朱伟明 E-mail:weimingzhu@ouc.edu.cn
  • 基金资助:

    国家自然科学基金(Nos.81561148012,U1501221,U1606403)资助项目.

Bioactive Natural Products from the Marine Sponge-Derived Nocardiopsis dassonvillei OUCMDZ-4534

Liu Haishan, Zhu Guoliang, Zhao Shuige, Fu Peng, Zhu Weiming   

  1. Key Laboratory of Marine Drugs, Ministry Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003
  • Received:2018-06-29 Revised:2018-08-08 Published:2018-09-05
  • Contact: 10.6023/cjoc201806045 E-mail:weimingzhu@ouc.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 81561148012, U1501221, U1606403).

拟诺卡氏菌(Nocardiopsis dassonvillei)OUCMDZ-4534分离自西沙贪婪倔海绵(Dysidea avara),其发酵提取物表现出生物碱显色、系列紫外吸收及抑菌和肿瘤细胞毒活性.从其发酵产物中分离到12个化合物.通过质谱(MS)、紫外(UV)、红外光谱(IR)、电子圆二色谱(ECD)、核磁共振(NMR)和化学计算等方法,首次确定了外消旋体1中对映体的绝对构型分别为(3aS,7aS)-3a-羟基-3a,7a-二氢苯并呋喃-2(3H)-酮(1a)和(3aR,7aR)-3a-羟基-3a,7a-二氢苯并呋喃-2(3H)-酮(1b),其它化合物依次被确定为吩嗪(2)、1-羟基吩嗪(3)、1-甲氧基吩嗪(4)、1,6-二羟基吩嗪(5)、1-羟基-6-甲氧基吩嗪(6)、1,6-二羟基吩嗪-5-氧化物(7)、2-(4-甲基-2,6-二羟基-3,5-二氯)苯甲酰基-3-甲氧基-5-羟基苯甲酸甲酯(8)、N-(2-羟基苯基)乙酰胺(9)、N-(2-羟基苯基)苯甲酰胺(10)、(E)-3-(4-羟基)苯丙烯酸(11)和(E)-3-(4-羟基-3-甲氧基)苯丙烯酸(12).化合物19分别对A549和K562细胞有选择性抑制作用,半数抑制浓度(IC50)分别为0.47和0.46 μmol·L-1;化合物4~8对K562、A549和MCF-7细胞表现出不同程度抑制作用,IC50值在0.02~1.48 μmol·L-1之间;化合物11对K562细胞以及化合物12对K562和MCF-7细胞有较强抑制活性,IC50分别为1.14、0.88和0.62 μmol·L-1.化合物78分别对烟曲霉(Aspergillus fumigates)和交替假单胞菌(Pseudoalteromonas nigrifaciens)有抑制活性,其最小抑菌浓度(MIC)分别为25.00和2.00 μg·mL-1.化合物4~69还表现出对甲型流感H1N1病毒的抑制活性,IC50分别为0.04、0.15、0.06和0.30 mmol·L-1.

关键词: 海洋放线菌, 达松维尔拟诺卡氏菌, 吩嗪衍生物, 肿瘤细胞毒活性, 抑菌活性, 抗流感病毒活性

Nocardiopsis dassonvillei OUCMDZ-4534 was isolated and identified from the sponge, Dysidea avara, from Xisha Islands of China. Compounds 1~12 were isolated from the fermenation broth of N. dassonvillei OUCMDZ-4534. By means of spectroscopic analysis, electronic circular dichroism (ECD) and 13C NMR calculations, their structures were identified as (3aS,7aS)-3a-hydroxy-3a,7a-dihydrobenzofuran-2(3H)-one (1a), (3aR,7aR)-3a-hydroxy-3a,7a-dihydrobenzofuran-2(3H)-one (1b), phenazine (2), 1-hydroxyphenazine (3), 1-methoxyphenazine (4), 1,6-dihydroxyphenazine (5), 1-hydroxy-6-methoxy-phenazine (6), 1,6-dihydroxy phenazin-5-oxide (7), dihydrogeodin (8), 2-acetamidophenol (9), 2-benzamidophenol (10), (E)-7-hydroxy cinnamic acid (11), and (E)-7-hydroxy-6-methoxycinnamic acid (12), respectively. This is the first time to resolve racemic-1 and identify the absolute structures of 1a and 1b. Compounds 1 and 9 displayed selective inhibition on A549 and K562 cell lines with the half maximal inhibitory concentration (IC50) of 0.47 and 0.46 μmol·L-1, respectively. Compounds 4~8 showed inhibitory activities against K562, A549 and MCF-7 cell lines with IC50 values ranging from 0.02 to 1.48 μmol·L-1. Compound 11 was cytotoxic to K562 while compound 12 was active against K562 and MCF-7 cell lines with the IC50 values of 1.14, 0.88 and 0.65 μmol·L-1, respectively. Compounds 7 and 8 showed antimicrobial activities against Aspergillus fumigatus and Pseudoalteromonas nigrifaciens with the minimum inhibitory concentration (MIC) of 25.00 and 2.00 μg·mL-1, respectively. Compounds 4~6 and 9 also exhibited inhibitions against the H1N1 virus with the IC50 values of 0.04, 0.16, 0.06 and 0.30 mmol·L-1, respectively.

Key words: marine actinobacterium, Nocardiopsis dassonvillei, phenazine analogues, cytotoxicity, antibacterial activity, anti-H1N1 virus activity