头孢美法仑的合成及其体外抗肿瘤活性研究

目的设计合成头孢美法仑，并对其进行体外抗肿瘤活性研究。方法以二苯甲酮、美法仑和7-苯乙酰胺基-3-氯甲基头孢烷酸对甲氧基苄酯（GCLE）为原料，经酯化、碘代、偶联、氧化、水解等反应得到目标化合物头孢美法仑，并采用MTT法对其进行体外抗肿瘤活性研究。结果设计并合成了目标产物头孢美法仑，利用MS和1H-NMR确证了结构；体外活性实验中，头孢美法仑在体外基本无毒，酶解后IC50为（101．97±1．705）μmol／L。结论头孢美法仑酶解后能够充分发挥细胞毒作用，而酶解前在体外基本无毒性，为颇具前景的前药，值得进一步研究。

Synthesis of cephalosporin and its antitumor activity in vitro

Objective To design and synthesize cephalosporin melphalan, and to evaluate its antitumor activity in vitro. Methods Benzophenone, melphalan, and 7-phenylacetamide-3-chloromethyl-3-cepham-4-carboxylic acid p-methyl-oxybenzyl ester （GCLE） were used as starting materials to synthesize the target compound cephalosporin melphalan by esterification, iodine, coupling, oxidation, and hydrolysis reactions. The antitumor activity in vitro was evaluated by MTT method. Results The target compound cephalosporin melphalan was synthesized and characterized by MS and IH-NMR. The antitumor activity experiments showed that cephalosporin melphalan was nontoxic in vitro, while after enzymolysis, the IC50 value was （101.97 ±1.705） μmol/L. Conclusion After enzymolysis, cephalosporin melphalan has the cytotoxic effect. While before enzymolysis, cephalosporin melphalan has been found to be nontoxic in vitro, which could be a valuable candidate for further development.