二氢叶酸还原酶抑制剂在肿瘤和细菌感染治疗中的研究进展  

Research advances on dihydrofolate reductase inhibitors in the treatment of tumors and bacterial infections

作　　者：陈灿彤 黄蕾 关霁晨 来芳芳 CHEN Can-tong;HUANG Lei;GUAN Ji-chen;LAI Fang-fang(State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物生物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2023年第10期2952-2960,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金面上项目(82173854)。

摘　　要：二氢叶酸还原酶(dihydrofolate reductase,DHFR)是治疗肿瘤、细菌感染和寄生虫感染的广为人知的关键靶点。DHFR在细胞DNA生物合成中发挥重要作用,其抑制剂通过抑制底物与DHFR结合,干扰一碳代谢,从而抑制细胞增殖。DHFR抑制剂的研究从20世纪40年代持续至今,已有多种DHFR抑制剂上市,主要用于抗肿瘤、抗菌、抗寄生虫和抗炎的治疗。本文以单靶点和双靶点为分类依据综述了近年来具有抗肿瘤或抗菌作用的DHFR抑制剂的研究进展,并展望了该领域研究所面临的机遇与挑战。Dihydrofolate reductase(DHFR)is a well-known key target in the treatment of tumors,bacterial infections,and parasitic infections;and it plays a critical role in the biosynthesis of cellular DNA.DHFR inhibitors interfere with one-carbon metabolism by inhibiting substrate binding to DHFR,thereby inhibiting cell proliferation.Research on DHFR inhibitors has continued since the 1940s.To date,a variety of DHFR inhibitors have come into the market,primarily used for anti-tumor,antibacterial,antiparasitic,and anti-inflammatory therapy.This review summarizes the research progress of DHFR inhibitors with antitumor or antibacterial effects in recent years based on the classification of single-target and dual-target and looks forward to the opportunities and challenges faced by the work in this field.

关 键 词：二氢叶酸还原酶 抗肿瘤 抗细菌感染 双靶点 二氢叶酸还原酶抑制剂 

分 类 号：R966[医药卫生—药理学]