海洋亚硫酸杆菌M44的代谢产物研究

Studies on the secondary metabolites of a marine Sulfitobacter sp.(M44)

目的研究一株海洋细菌M44的化学成分。方法采用ODS C18反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱以及高效液相色谱等分离手段对发酵得到的乙酸乙酯相进行分离、纯化;利用理化性质和波谱学分析对单体化合物进行结构鉴定并用MTT法评价其体外细胞毒活性。结果从海洋细菌Sulfitobacter sp.(M44)发酵物中分离得到6个环二肽类化合物,分别鉴定为Cyclo-(L-Leu-D-val)(1)、Cyclo-(L-Phe-D-val)(2)、Cyclo-(L-Phe-L-Leu)(3)、Cyclo-(L-Leu-L-Ile)(4)、Cyclo-(D-Phe-L-Ile)(5)、Cyclo-(L-Trp-L-Pro)(6)。体外活性实验表明:化合物2,4对HepG2细胞株均表现出一定的生长抑制活性,其IC50分别为88μg/mL和105μg/mL,其中化合物4还对Hep2细胞株表现出生长抑制活性,其IC50为115μg/mL。结论以上化合物均为首次从该属细菌的代谢产物中分离得到,为进一步开发利用东海微生物资源奠定了一定的基础。

Objective To study the secondary metabolites of marine-derived Sulfitobacter sp. （M44）. Methods The ethyl acetate （EtOAc） extract of fermentation broth was subjected to chromatography on Sephadex LH-20, ODS C18 reversed-phase column and high-performance liquid chromatography for constituents. The structures of the compounds were elucidated by 1HNMR, 13CNMR and MS technologies; MTT method were employed to detect the biological activities of the separated compounds. Results Six cyclodipeptides were obtained from the Sulfitobacter sp. （M44） and their structures were identified as follows： Cyclo（L-Leu-D-val）（1）, Cyclo（L-Phe-D-val） （2）, Cyclo（L- Phe-L-Leu） （3）, Cyelo（L-Leu-L-Ile） （4）, Cyclo（D-Phe-L-Ile） （5） and Cyclo（L-Trp-L-Pro） （6）. Cytotoxic activities tests showed that compound 2 and 4 can inhibit the growth of HepG2 cell with IC50 values being 88ug/mL and 105ug/mL respectively, and compound 4 also showed some inhibitory activities against Hep2 cell with IC50 value being 115ug/mL. Conclusion All the six compounds were isolated from Sulfitobacter sp. for the first time. The present study provided a basis for further exploiting microorganism of the East China Sea.