14β-侧链紫杉醇衍生物的合成及抗肿瘤活性

SYNTHESIS AND ANTITUMOR ACTIVITY OF TAXOL DERIVATIVES WITH 14β-SIDE CHAIN

为了寻找高效低毒、抗瘤谱广、综合性能好又不依赖自然资源的新一代紫杉醇类抗癌药 ,以组织培养得到的紫杉烷 sinenxan A为最初起始原料 ,以中间体 6为本文合成原料分别经 5步和 6步合成了两个新的 14β-侧链紫杉醇衍生物 ,并首次观察到紫杉烷的 10位羰基 / 9位羟基在硅胶中转变为 10位羟基 / 9位羰基。将目标化合物进行了抗肿瘤体外试验和微管聚合试验。结果表明 ,这两个化合物对 KB细胞的 IC50 >10 μg,在浓度为 10 μM时对微管无聚合作用。

In order to develop new generation of taxol like anticancer agents with fewer side effects,improved activity,superior pharmacological properties and broad antitumor spectrum,two new taxol derivatives with 14β side chain were synthesized from taxane intermediate 6,which was derived from sinenxan A a biosynthetic taxane.Target compounds 4 and 5 were tested in a tubulin assembly assay,and in an in vitro cytotoxicity assay(KB cell line).Compared with taxol,they showed significantly decreased activity in the cytotoxicity assay in vitro against KB.In tubulin assembly assay they did not show any activity at 10μM.