叶酸依赖性酶抑制剂的抗肿瘤活性

Advances in folate-dependent enzyme inhibitors as antitumor agents

叶酸依赖性酶以四氢叶酸衍生物为辅酶,在细胞DNA的生物合成中发挥重要作用。叶酸依赖性酶抑制剂通过抑制叶酸依赖性酶与正常底物的结合,干扰一碳代谢与叶酸代谢,阻碍DNA的生物合成,从而导致肿瘤细胞死亡。作为抗肿瘤药物作用靶点的叶酸依赖性酶,主要包括二氢叶酸还原酶、胸苷酸合成酶、甘氨酰胺核糖核苷酸甲酰基转移酶和咪唑甲酰胺核苷酸甲酰转移酶等。本文根据酶的分类,综述近年来叶酸依赖性酶抑制剂的抗肿瘤药物的研究进展。

Tetrahydrofolate derivatives are coenzymes of the folate-dependent enzymes,which play important roles in cellular DNA biosynthesis.Folate-dependent enzyme inhibitors cause the death of cancer cells through inhibiting the binding of folate-dependent enzymes with normal substrate and disturbing the one-carbon and folic acid metabolism to prevent the biosynthesis of DNA.Folate-dependent enzymes as anticancer drug targets mainly involve dihydrofolate reductase（DHFR）,thymidylate synthase（TS）,glycinamide ribonucleotide formyltransferase（GARFT） and aminoimidazole carboxamide ribonucleotide formyltransferase（AICARFT）.The latest advances in antitumor activities of different folate-dependent enzyme inhibitors were described in this review.