目的 設(shè)計(jì)合成美法侖-甘草次酸復(fù)合物，并對其體內(nèi)外抗腫瘤活性進(jìn)行研究。方法 以美法侖和18α-甘草次酸為原料，通過酯化、氧化、?；涂s合反應(yīng)制備目標(biāo)化合物3a和3b，結(jié)構(gòu)經(jīng)元素分析、MS、¹H-NMR確證，并采用MTT法對其體外抗腫瘤活性進(jìn)行研究，同時(shí)考察了其對正常大鼠肝細(xì)胞BRL和小鼠成纖維細(xì)胞L929的細(xì)胞毒性。結(jié)果 目標(biāo)化合物3a、3b的體外抗腫瘤活性明顯優(yōu)于母體藥物18α-甘草次酸和美法侖，且對正常細(xì)胞的毒性小于氮芥類藥物美法侖。結(jié)論 美法侖-甘草次酸復(fù)合物3a和3b抗腫瘤活性良好，具有開發(fā)成抗腫瘤候選藥物的前景。

Objective To design and synthesize melphalan-glycyrrhetinic acid complexes, and evaluate its antitumor activity in vitro. Methods Melphalan and 18α-glycyrrhetinic acid were used as starting materials to synthesize the target compounds 3a and 3b by esterification, oxidation, acylation, and condensation reaction. The target compounds were characterized by elemental analyses, MS, and ¹H-NMR. The antitumor activities in vitro were evaluated by MTT method. The cytotoxicity of target compounds against normal BRL and L929 cells were also evaluated. Results The in vitro antitumor activity experiments showed that the antitumor activities of target compounds 3a and 3b were higher than those of parent drugs, 18α-glycyrrhetinic acid, and melphalan, and less toxicity than melphalan. Conclusion Melphalan-glycyrrhetinic acid complexes 3a and 3b exhibit high antitumor activity, which have the prospect for development into anticancer drugs.

天津市衛(wèi)生局科技基金資助項(xiàng)目（2014KY38）