环巴胺类似物的合成及体外抗肿瘤细胞活性研究

Synthesis and Antitumor Activity of Cyclopamine Analogues

环巴胺是一种选择性抑制Hedgehog信号通路的甾体生物碱,具有显著的抗肿瘤活性。为研究环巴胺类似物抗肿瘤作用的构效关系,本文以介芬胺为原料,采用选择性还原、甲基化及氧化反应合成了环巴胺及8个类似物,其中化合物4、9、10的结构未见文献报道。运用MS、NMR对产物进行了结构表征,以MTT法研究产物对人胰腺癌Aspc-1和人胃癌SGC-7901细胞体外增殖的抑制作用,结果化合物5对两种细胞均有抑制作用,但活性略低于环巴胺。

Cyclopamine is a steroid alkaloid with Hedgehog signal pathway inhibitory activity and exhibits significant antitumoractivity. In this study,cyclopamine analogues were synthesized by reduction,oxidation and methylation from an available alkaloid,jervine. The structures of the yielded compounds were determined by MS,1D and 2D NMR. Structures of compounds 4,9 and 10 have not been reported previously. The antitumor activities of the 10 synthesized compounds against Aspc-1 and SGC-7901 cancer cells were evaluated by MTT method.