一株昆虫内生真菌 Alternaria sp畅次级代谢产物研究

摘要

采用硅胶柱色谱，Sephadex LH-20凝胶柱色谱及HPLC等方法从昆虫共生真菌Alternaria sp.（Be-1）的发酵液分离得到7个代谢产物，经NMR，MS及理化性质等确定为4个环肽和3个聚酮类化合物，4-甲氧基格链孢酚（1），5′-methoxy-6-methyl-biphenyl-3，4，3′-triol（2），altenusin（3），二氢腾毒素（4），腾毒素（5），环（4-羟基-脯-亮）二肽（6）和cyclo（L-Phenylalanine-trans-4-hydroxy-L-proline）（7）。测定了化合物1-7对抗肿瘤治疗靶点-受体酪氨酸激酶的抑制活性，药理实验结果表明，化合物1-6对三种酪氨酸激酶（EGFR，VEGFR-1，c-Met）具有不同程度的抑制活性，化合物1，3，6对EGFR，VEGFR-1，c-Met均具有强的抑制作用，而且化合物6还有选择性抑制EGFR和c-Met的活性。%Seven secondary metabolites were isolated from the endophytic fungus Alternaria sp.(Be-1) by silica gel,Sephadex LH-20 chromatography and HPLC.Their structures were elucidated as alternariol 4-O-methyl ether(1),5′-methoxy-6-methyl-biphenyl-3,4,3′-triol(2),altenusin(3),tentoxin(4),dihydrotentoxin(5),cyclo(4-hydroxyl-Pro-Leu)(6), cyclo(L-Phenylalanine-trans-4-hydroxy-L-proline)(7)by NMR and MS.The activity assay showed that compounds 1-6 displayed inhibitory activities against the three targets of tyrosine kinases (EGFR,VEGFR-1,c-Met),and compounds 1,3 and 6 showed strong inhibiting activities to EGFR, VEGFR-1,c-Met.At last,compound 6 displayed selectively inhibitory activity to EGFR and c-Met.