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 a synthetic melphalan-glycyrrhetic acid complex and study its antitumor activity in vitro and in vivo. Methods The target compounds 3a and 3b were prepared by esterification, oxidation, acylation and condensation reactions using melphalan and 18α-glycyrrhetinic acid as starting materials. Their structures were confirmed by elemental analysis, MS and 1H-NMR. Their structures were characterized by MTT In vitro antitumor activity were studied, and its cytotoxicity to normal rat hepatocytes BRL and mouse fibroblast L929 was also investigated. Results The target compounds 3a and 3b showed significantly better in vitro antitumor activity than the parent drug 18α-glycyrrhetinic acid and melphalan, and had less toxicity to normal cells than the nitrogen mustard melphalan. Conclusion The anti-tumor activity of melphalan-glycyrrhetic acid complexes 3a and 3b is good and has the prospect of developing antitumor drug candidates.