State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Lung Cancer Center, Laboratory of Lung Cancer, Western China Hospital of Sichuan University.
Eur J Med Chem. 2020 Jun 1;195:112268. doi: 10.1016/j.ejmech.2020.112268. Epub 2020 Apr 1.
Drug-resistant bacteria pose an increasingly serious threat to mankind all over the world. However, the currently available clinical treatments do not meet the urgent demand.Therefore, it is desirable to find new targets and inhibitors to overcome the problems of antibiotic resistance. Dihydrofolate reductase (DHFR) is an important enzyme required to maintain bacterial growth, and hence inhibitors of DHFR have been proven as effective agents for treating bacterial infections. This review provides insights into the recent discovery of antimicrobial agents targeting DHFR. In particular, three pathogens, Escherichia coli (E. coli), Mycobacterium tuberculosis(Mtb) and Staphylococcus aureus(S. aureus), and research strategies are emphasized. DHFR inhibitors are expected to be good alternatives to fight bacterial infections.
耐药菌对全世界的人类构成了日益严重的威胁。然而，目前可用的临床治疗方法无法满足这一迫切需求。因此，人们希望找到新的靶标和抑制剂来克服抗生素耐药性的问题。二氢叶酸还原酶（DHFR）是维持细菌生长所必需的重要酶，因此 DHFR 的抑制剂已被证明是治疗细菌感染的有效药物。本综述提供了有关针对 DHFR 的抗菌剂的最新发现的见解。特别是，强调了三种病原体，即大肠杆菌（E. coli）、结核分枝杆菌（Mtb）和金黄色葡萄球菌（S. aureus），以及研究策略。DHFR 抑制剂有望成为对抗细菌感染的良好替代品。
