20-位酯化喜树碱衍生物的合成和抗肿瘤活性

Synthesis and antitumor activity of 20-O-linked camptothecin ester derivatives

摘要: 目的寻找高效低毒的抗肿瘤新喜树碱酯衍生物。方法通过酰化反应合成了目标产物，用¹HNMR,IR,MS,和 HRMS确证了它们的结构；MTT法评价了目标产物的细胞毒活性；并用小鼠肝癌H₂₂肿瘤模型对这些化合物的体内抗肿瘤活性进行了评价。结果合成了12个新喜树碱衍生物。结论体内外抗肿瘤试验表明，对小鼠肝癌细胞H₂₂模型，新合成的喜树碱衍生物4的抗肿瘤活性与拓扑替康相近，但毒性低于拓扑替康。

Abstract: AimTo improve the profile of 20(S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed. MethodsThese derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with ¹HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H₂₂ in mice. ResultsTwelve derivatives of camptothecin ester are new compounds. Conclusionin vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H₂₂ mouse liver tumoral model.