目的 设计并合成甘草次酸C₃、C₃₀衍生物, 并对其体外抗肿瘤活性进行研究。方法 以甘草次酸为先导化合物, 对其C₃位羟基、C₃₀位羧基进行结构修饰, 并采用SRB法对目标化合物进行体外抗肿瘤活性研究。结果 设计合成了12个新型甘草次酸衍生物, 并利用MS、¹H-NMR及元素分析确证了结构;体外实验中, 目标化合物对MCF-7和A549肿瘤细胞的抑制活性均明显强于甘草次酸, 其中化合物GA-I₁、GA-I₂和GA-II₁对MCF-7和A549两种细胞表现出很好的抑制活性, 明显高于对照药吉非替尼。结论 甘草次酸衍生物具有良好的抗肿瘤活性, 值得进一步研究。

Objective To design and synthesize glycyrrhetinic acid C₃ and C₃₀ derivatives and their antitumor activities in vitro. Methods Glycyrrhetinic acid was used as starting material to synthesize the target compounds by structural modification at C₃ hydroxyl group, and C₃₀ carboxyl group. The antitumor activities of the compounds were tested by SRB assay. Results Twelve novel glycyrrhetinic acid derivatives were synthesized and characterized by MS, ¹H-NMR, and elemental analysis. The in vitro antitumor activity experiments showed that cytotoxic effects of target compounds against MCF-7 and A549 cells were higher than those of glycyrrhetinic acid in vitro. In which compounds GA-I₁, GA-I₂, and GA-II₁ had better cytotoxic effects against MCF-7 and A549 cells, and it was better than control drug gefitinib. Conclusion The target compounds glycyrrhetinic acid derivatives have good antitumor activities which could be a valuable candidate for further development.

国家自然科学基金资助项目(21372156);辽宁省教育厅高等学校优秀人才支持计划资助项目(LR2013017);沈阳市科技计划资助项目(F13-316-1-47)