Screening and Identification of a Novel Anti-tuberculosis Compound That Targets Deoxyuridine 5'-Triphosphate Nucleotidohydrolase.

ABSTRACT: Tuberculosis (TB) is still a threat to humans worldwide. The rise of drug-resistant TB strains has escalated the need for developing effective anti-TB agents. Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is essential for thymidylate biosynthesis to maintain the DNA integrity. In Mycobacterium tuberculosis, dUTPase provides the sole source for thymidylate biosynthesis, which also has the specific five-residue loop and the binding pockets absent in human dUTPase. Therefore, dUTPase has been regarded as a promising anti-TB drug target. Herein, we used a luminescence-based dUTPase assay to search for the inhibitors target M. tuberculosis dUTPase (Mt-dUTPase) and identified compound F0414 as a potent Mt-dUTPase inhibitor with an IC₅₀ of 0.80 ± 0.09 μM. F04

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8544286 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature