紫杉醇构效关系及类似物生物活性的研究进展

Advances in Structure-Activity Relationship of Paclitaxel and Bioactivity of Analogues

紫杉醇是当今最有效的抗癌药物之一.它的作用机理独特,通过诱导和促进微管蛋白聚合形成稳定结构,从而抑制微管解聚.对紫杉醇的构效与活性之间的关系以及近十年来紫杉醇类似物研究进展进行了比较详尽的阐述,包括以下几个方面:C2位苯甲酰基、C4位乙酰基、D环、C13侧链、C2与C3′成环、C4与C3′成环以及其它位基团对紫杉醇生物活性的影响.从紫杉醇的构效关系看,C1、C7、C9和C10位基团对它的生物活性并无太大的影响,但是C2、C4位的基团以及D环和C13位的侧链对紫杉醇的生物活性影响重大.

Paclitaxel is considered one of the most promising antitumor druggery, h possesses a unique mechanism of action as promoters of tubulin aseembly and inhibitors of microtubule disassembly. We make a comprehensive summary of the relationship between the structure-effect of paclitaxel and its bioactivity and studies of paclitaxel＇ s analogues. Topics discussed include： effects of C2-benzoyl, CA-acetate, D-ring, C13 side chain, C2 -C3＇-linked macrocyclic, C4 - C3＇-linked maerocyclic and other groups on bioaetivity of paclitaxel. From structure-effect relationship of paclitaxel, groups of C1, C7, C9 and C10 have weaker effect on its bioactivity, while C2-benzoyl, C4-acetate, D- ring and C13 side chain have stronger effect on it.