Dihydrofolate reductase inhibitors for use as antimicrobial agents.

Juan He, Wenliang Qiao, Qi An, Tao Yang, Youfu Luo

Journal: European journal of medicinal chemistry 2020;195():112268

PMID: 32298876

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: 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.; Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].; 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. Electronic address: [email protected].

DOI: 10.1016/j.ejmech.2020.112268

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MeSH Terms: Anti-Infective Agents, Folic Acid Antagonists, Tetrahydrofolate Dehydrogenase