藤黄酰甘氨酸的合成及体外抗肿瘤活性测试

Synthesis and Biological Evaluation of Gambogoyl Glycine as Anticancer Agent

以藤黄酸和甘氨酸甲酯为原料,采用N-乙基-N-二甲胺基丙基碳二亚胺(EDCI)法合成藤黄酰甘氨酸甲酯,再经水解得到藤黄酰甘氨酸。目标化合物的化学结构经红外光谱、核磁共振氢谱及质谱确证。考察了反应溶剂、反应温度、反应液pH值三个因素对水解反应产率的影响,优选出最佳合成工艺。最佳合成工艺为:反应溶剂为丙酮-水体系、反应温度25～30℃、反应液pH值为10～11。藤黄酰甘氨酸收率达70%(以藤黄酸计)。采用溴化噻唑蓝四氮唑(MTT)法测试目标物的体外抗肿瘤活性,结果表明,藤黄酸酰甘氨酸具有很好的抗肿瘤作用。

In order to search for new compound with higher anti-tumor activity and lower toxicity, glycine conjugate of gambogic acid was designed and synthesized. Gambogoyl glyeine was gained by. coupling the corresponding glyein methylate to the 30-COOH of gambogic acid and subsequent deacetylation. The effect of solvent, reaction temperature and pH on the yield of gambogoyl glycine was studied. The optimum reaction conditions were as follows ： acetone-water as the solvent; keeping temperature at 25-30℃; and pH= 10 - 11. The yield of the target compound was 70%. The biological evaluation showed that gambogoyl glyeine had stronger cytotoxic activities than gambogic acid against human hepatoma cells BEL- 7402 in vitro by MTT method.