海洋真菌烟曲霉Aspergillus fumigatus YK-7次级代谢产物的分离鉴定及抗肿瘤活性

摘要

The secondary metabolites of marine-derived fungus Aspergillus fumigatus YK-7 were studied.Chromatographic techniques were used for the isolation and purification,including silica gel,ODS,Sephadex LH-20 column chromatography and HPLC.The structures were identified on the basis of physicochemical properties and spectroscopic analysis.Ten compounds were obtained and their structures were identified as chaetominine (1),(-)-11-epi-chaetominine(2),fumiquinazoline A (3),fumiquinazoline B (4),fumiquinazoline C (5),fumiquinazoline F (6),fumiquinazoline G (7),fumiquinazoline J (8),bis-N-norgliovictin (9),and 2-methylthio-cyclo (Phe-Ser) (10).Compounds 1 and 2 were isolated from marine-derived fungus Aspergillus fumigatus for the first time.Antiproliferative effects of compounds on human leukemic monocyte lymphoma cell line U937 and human prostate cancer PC-3 cell lines were measured in vitro.Compounds 3,6,7 and 8 exhibited moderate cell growth inhibitory activities against U937 cell line,with the IC50 values of 87.1,16.4,33.3,and 8.6 μmol · L-1,respectively.Compound 8 exhibited moderate cell growth inhibitory activity against PC-3 cell line,with the IC50 value of 58.5 μmol·L-1.%目的 研究海洋真菌烟曲霉Aspergillus fumigatus YK-7次级代谢产物,以期获得活性先导化合物.方法 采用硅胶柱色谱、ODS柱色谱、凝胶柱色谱、高效液相色谱等方法进行分离纯化,通过理化性质和波谱数据分析鉴定化合物的结构.采用台盼蓝法和MTT法进行抗肿瘤活性测试.结果 从烟曲霉的真菌发酵液的乙酸乙酯萃取物和菌丝体的丙酮提取物中分离得到10个生物碱类化合物,分别鉴定为chaetominine(1)、(-)-11-epi-chaetominine (2)、fumiquinazoline A(3)、fumiquinazoline B(4)、fumiquinazoline C(5)、fumiquinazoline F(6)、fumiquinazoline G(7)、fumiquinazoline J(8)、bis-N-norgliovictin(9)、2-methylthio-cyclo (Phe-Ser)(10).体外抗肿瘤活性测试结果显示,化合物3、6、7、8对人单核细胞白血病细胞(U937)的IC50值分别为87.1、16.4、33.3、8.6μmol· L-;化合物8对人前列腺癌细胞(PC-3)的IC50值为58.5 tμmol·L-1.结论 化合物1、2为首次从海洋来源烟曲霉中分离得到.化合物3、6、7、8对选定的人肿瘤细胞U937和PC-3具有一定的体外抗增殖活性.