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

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

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1和9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7和8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4~6和9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.

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.