目的 设计合成美法仑-甘草次酸复合物，并对其体内外抗肿瘤活性进行研究。方法 以美法仑和18α-甘草次酸为原料，通过酯化、氧化、酰化和缩合反应制备目标化合物3a和3b，结构经元素分析、MS、¹H-NMR确证，并采用MTT法对其体外抗肿瘤活性进行研究，同时考察了其对正常大鼠肝细胞BRL和小鼠成纤维细胞L929的细胞毒性。结果 目标化合物3a、3b的体外抗肿瘤活性明显优于母体药物18α-甘草次酸和美法仑，且对正常细胞的毒性小于氮芥类药物美法仑。结论 美法仑-甘草次酸复合物3a和3b抗肿瘤活性良好，具有开发成抗肿瘤候选药物的前景。

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.

天津市卫生局科技基金资助项目（2014KY38）