Identification of potential inhibitors of dihydrofolate reductase (DHFR) through blocking the folate biosynthetic pathway of <i>Mycobacterium tuberculosis</i> utilizing structure-based virtual screening.

ABSTRACT: Tuberculosis (TB) has emerged as a leading cause of death due to a single infectious agent-Mycobacterium tuberculosis (Mt). This situation is exacerbated by delayed diagnosis, inadequate administration of effective TB medications, prolonged duration of treatment, shortage of toxin-free TB drugs, and frequent increases in resistance to most TB drugs. In an urge to find potential drug candidates for the treatment of fatal infectious TB disease, we targeted the folate biosynthetic pathway that involves the ubiquitous enzyme dihydrofolate reductase (DHFR), which catalyzes the NADPH-dependent reduction of dihydrofolate with the generation of tetrahydrofolate (THF). Blocking the enzymatic activity of DHFR exhausts the cellular pool of THF, which results in cessation of DNA synthesis in ra

SUBMITTER: Halder SK 

PROVIDER: S-EPMC12486253 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature