姜黄素-二氯乙酸偶联物的合成及抗肿瘤活性研究

SYNTHESIS AND ANTI-TUMOR ACTIVITY OF CONJUGATE OF CURCUMIN AND DICHLOROACETIC ACID

以二氯乙酸为起始原料通过制备酰氯后与姜黄素反应制得姜黄素-二氯乙酸偶联物。采用噻唑兰(MTT)法考察其对HeLa、HepG2、A2780及A549等4种肿瘤细胞的增殖抑制活性,通过线粒体膜电位检测试剂盒(JC-1)检测其对线粒体膜电位的破坏,通过流式细胞术检测其诱导的细胞凋亡。结果发现姜黄素-二氯乙酸偶联物抗肿瘤活性比单纯的姜黄素、二氯乙酸及姜黄素与二氯乙酸的混合物更强,且能更强地破坏线粒体膜电位及诱导细胞凋亡。可见姜黄素-二氯乙酸偶联物表现出显著的协同效应,具有潜在的药物开发价值。

Using dichloroacetic acid as starting material to prepare dichloroacetyl chloride,conjugate of curcumin and dichloroacetic acid was synthesized through reaction between curcumin and dichloroacetyl chloride.The in vitro antitumor activities of the conjugate was evaluated for HeLa,HepG2,A2780 and A 549 by MTT.Damage of mitochondrial membrane potential was measured by mitochondrial membrane potential assay kit with JC-1 and apoptosis of cells were assayed by flow cytometry methods.The results showed that the antitumor activity of conjugate of curcumin and dichloroacetic acid was more potent than those of curcumin,dichloroacetic acid or mixture of curcumin and dichloroacetic acid,moreover,it can destruct mitochondrial membrane potential and induce apoptosis of cells,more strongly.It is evident that conjugate of curcumin and dichloroacetic acid has significant synergistic effects,with a potential value of drug development.