海洋放线菌Nocardiopsis sp. SCSIO 11492的抗肿瘤活性成分研究

Antitumor compounds from marine actinomycete Nocardiopsis sp. SCSIO 11492

目的研究海洋放线菌Nocardiopsis sp.SCSIO 11492的抗肿瘤活性成分。方法采用ODS反相硅胶中压柱色谱、正相硅胶柱色谱、Sephadex LH-20凝胶柱色谱等方法分离纯化次级代谢产物;13C NMR、1H NMR、HSQC、1H-1HCOSY、HMBC等波谱技术并结合电喷雾电离质谱法鉴定结构;MTT法进行体外抗肿瘤活性测试。结果从海洋放线菌Nocardiopsis sp.SCSIO 11492的乙酸乙酯萃取物中分离得到8个化合物,分别为2'-脱氧腺苷(1)、2'-脱氧胸腺嘧啶核苷(2)、2'-脱氧尿苷(3)、尿嘧啶核苷(4)、1-棕榈酰-3-β-D-半乳糖甘油酯(5)、环(亮-缬)二肽(6)、环(缬-脯)二肽(7)、环(脯-脯)二肽(8)。其中化合物5对小鼠单核巨噬细胞白血病细胞RAW264.7显示出较好的生长抑制活性(IC50=10.9μmol/L),其他化合物均没有表现出明显的细胞毒活性(IC50>20.0μmol/L)。结论以上8个化合物均为首次从该菌中分离得到,其中化合物5可能是该菌的抗肿瘤活性成分。

Objective To obtain cytotoxic secondary metabolites from a marine actinomycete Nocardiopsis sp. SCSIO 11492. Methods The secondary metabolites were isolated and purified by medium performance liquid chromatography （ MPLC ） over silica gel, ODS, and Sephadex LH-20; their structures were elucidated by nuclear magnetic resonane（1H-NMR,13 C-NMR）,heteronuclear single-quantum correlation （ HSQC ） ,1 H-1 H correlation spectroscopy （ 1 H-1 H COSY ） , heteronuclear multiple-bond correlation （HMBC）,and electrospray Ionization-mass spectrum （ESI-MS）. Results Eight compounds were isolated from ethyl acetate crude extract of Nocardiopsis sp. SCSIO 11492. These compounds were identified as 2′-deoxyadenosine （ 1 ） , 2′-deoxythymidine （ 2 ） , 2′-deoxyuidine （ 3 ） , uridine （ 4 ） , 1-palmitoyl-3-D-galactosyl-sn-glycerol spongilipid （5）,cyclo-（Leu-Val） （6）, cyclo-（L-Val-L-Pro） （7）,and cyclo-（Pro-Pro） （8）. Among these isolates,compound 5 exhibited moderate cytotoxic activity against human tumor RAW264.7 cells with IC50 value of 10.9 μmol/L,while others showed negative effect （IC50﹥20.0 μmol/L） . Conclusion It was the first time to report the compounds from Nocardiopsis sp. SCSIO 11492. And compound 5 might be the main antitumor component of this strain.