Computational Development of Inhibitors of Plasmid-Borne Bacterial Dihydrofolate Reductase.

ABSTRACT: Resistance to trimethoprim and other antibiotics targeting dihydrofolate reductase may arise in bacteria harboring an atypical, plasmid-encoded, homotetrameric dihydrofolate reductase, called R67 DHFR. Although developing inhibitors to this enzyme may be expected to be promising drugs to fight trimethoprim-resistant strains, there is a paucity of reports describing the development of such molecules. In this manuscript, we describe the design of promising lead compounds to target R67 DHFR. Density-functional calculations were first used to identify the modifications of the pterin core that yielded derivatives likely to bind the enzyme and not susceptible to being acted upon by it. These unreactive molecules were then docked to the active site, and the stability of the docking poses of the b

SUBMITTER: Silva PJ 

PROVIDER: S-EPMC9220120 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature