Dihydrofolate reductase inhibitors for use as antimicrobial agents

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

doi:10.1016/j.ejmech.2020.112268

Dihydrofolate reductase inhibitors for use as antimicrobial agents

Eur J Med Chem. 2020 Jun 1:195:112268. doi: 10.1016/j.ejmech.2020.112268. Epub 2020 Apr 1.

Authors

Juan He¹, Wenliang Qiao², Qi An¹, Tao Yang³, Youfu Luo⁴

Affiliations

¹ 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.
² Lung Cancer Center, Laboratory of Lung Cancer, Western China Hospital of Sichuan University.
³ Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: michael_2012@126.com.
⁴ 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: luo_youfu@scu.edu.cn.

PMID: 32298876
DOI: 10.1016/j.ejmech.2020.112268

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.

Keywords: Bacterial infections; DHFR; Escherichia coli; Mycobacterium tuberculosis; Staphylococcus aureus.

Publication types

Review

MeSH terms

Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology*
Folic Acid Antagonists / chemistry
Folic Acid Antagonists / pharmacology*
Tetrahydrofolate Dehydrogenase / chemistry
Tetrahydrofolate Dehydrogenase / metabolism*

Substances

Anti-Infective Agents
Folic Acid Antagonists
Tetrahydrofolate Dehydrogenase