海洋芽孢杆菌次生代谢产物的分离、鉴定及生物学活性的初步研究

Isolation,identification and biological characterization of secondary metabolites produced by a marine Bacillus subtilis

目的:开发药用海洋微生物资源,从微生物代谢产物中获取活性物质。方法:利用硅胶柱、凝胶柱、高效液相等色谱技术对抗菌模型筛选到的活性菌株F81612发酵液的乙酸乙酯浸膏进行分离,通过1HNMR、13CNMR和MS对化合物进行结构鉴定,利用纸片法和四甲基偶氮唑盐比色法对单体化合物进行生物学活性评价。结果和结论:分离鉴定了11个化合物,它们分别为:macrolactinA(1),3-羟基乙酰基吲哚(2),3-吲哚乙醇(3),环(色-脯)二肽(4),环(异亮-色)二肽(5),环(亮-脯)二肽(6),环(亮-缬)二肽(7),环(异亮-脯)二肽(8),环(苯丙-缬)二肽(9),N-苯乙基乙酰胺(10),对羟基苯甲醛(11)。化合物1为主要活性成分,对稻瘟霉、大肠杆菌、金黄色葡萄球菌的MIC值分别为3.6、0.45和6.3μg/ml,对肿瘤细胞株HeLa及HepG2的IC50值分别为2.0和1.8μg/ml。

Objective：To exploit marine microorganisms and study their secondary metabolites for new drugs. Methods： An antibacterial model was used to screen for active strains. The ethyl acetate （EtOAc） extract was separated by silica chromatography, gel filtration chromatography, and high-performance liquid chromatography. The structures of the compounds were elucidated by 1HNMR, 13CNMR and MS technologies; Kirby-Bauer Disc Diffusion method and MTT method were employed to detect the biological activities of the separated compounds. Results： Eleven compounds were separated and identified as macrolactin A （1）, 3-Hydroxyl acetyl-indole （2）, 3-indolethano） （3）, eyclo-（Try-Pro） （4）, cyclo-（Ile-Try） （5）, cyclo- （Leu-Pro） （6）, cyclo-（Leu-Val） （7）, cyclo-（Ile-Pro） （8）, cyclo-（Phe-Val） （9）, N- phenethylacetamide （10）, P-hydroxy benzaldehyde （PHB） （11）. Conclusion： Compound 1 shows strong inhibitory activities against Pyricularia oryzae, Escherichia coli and Staphylococcus aureus （with MIC values being 3.6, 0.45 and 6.3 μg/ml, respectively）, and tumor cell lines HeLa and HepG2 （with the IC50 values being 2.0 and 1.8 μg/ml, respectively）.