甘草次酸C3、C30衍生物的合成及其体外抗肿瘤活性研究

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。

Synthesis of glycyrrhetinic acid C3 and C30 derivatives and their antitumor activities in vitro

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.