目的 設(shè)計并合成甘草次酸C₃、C₃₀衍生物, 并對其體外抗腫瘤活性進(jìn)行研究。方法 以甘草次酸為先導(dǎo)化合物, 對其C₃位羥基、C₃₀位羧基進(jìn)行結(jié)構(gòu)修飾, 并采用SRB法對目標(biāo)化合物進(jìn)行體外抗腫瘤活性研究。結(jié)果 設(shè)計合成了12個新型甘草次酸衍生物, 并利用MS、¹H-NMR及元素分析確證了結(jié)構(gòu);體外實驗中, 目標(biāo)化合物對MCF-7和A549腫瘤細(xì)胞的抑制活性均明顯強于甘草次酸, 其中化合物GA-I₁、GA-I₂和GA-II₁對MCF-7和A549兩種細(xì)胞表現(xiàn)出很好的抑制活性, 明顯高于對照藥吉非替尼。結(jié)論 甘草次酸衍生物具有良好的抗腫瘤活性, 值得進(jìn)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.

國家自然科學(xué)基金資助項目(21372156);遼寧省教育廳高等學(xué)校優(yōu)秀人才支持計劃資助項目(LR2013017);沈陽市科技計劃資助項目(F13-316-1-47)