相转移催化法合成喜树碱糖苷及其对Topo I抑制活性

Synthesis of camptothecin glycosides by phase transfer-catalysis and its inhibitory activity against Topo I

摘要: 目的寻找高效低毒的喜树碱类抗肿瘤新药。方法采用相转移催化法合成了6个喜树碱糖苷衍生物(7～12)，经¹H NMR，IR和MS分析确证了化合物的结构。采用MTT法考察了所合成的喜树碱糖苷对肿瘤细胞抑制活性，采用分子生物学手段考察了所合成的喜树碱糖苷衍生物对Topo I的抑制活性。结果和结论相转移催化法大大提高了喜树碱糖苷的合成收率，喜树碱糖苷类化合物对肿瘤细胞的体外抑制活性较喜树碱母核显著降低，但仍保持很好的Topo I抑制活性。

Abstract: AimTo find new anticancer drug based on the structure of 10-hydroxy camptothecin. MethodsSix camptothecin glycosides (7-12) were synthesized by phase transfer catalysis. The structures of all compounds synthesized were determined by ¹H NMR, IR and MS. Their antitumor activity was evaluated on cancer cells in vitro, and inhibitory activity against Topo I was evaluated by molecular biologic method. Results and ConclusionThe result indicated that the yield of camptothecin glycosides by phase transfer catalysis is much higher than by the method from literature, camptothecin glycosides have much lower cytotoxicities on cancer cell in vitro, but have better inhibitory activity of Topo I.