A Series of Spiropyrimidinetriones that Enhances DNA Cleavage Mediated by Mycobacterium tuberculosis Gyrase.

ABSTRACT: The rise in drug-resistant tuberculosis has necessitated the search for alternative antibacterial treatments. Spiropyrimidinetriones (SPTs) represent an important new class of compounds that work through gyrase, the cytotoxic target of fluoroquinolone antibacterials. The present study analyzed the effects of a novel series of SPTs on the DNA cleavage activity of Mycobacterium tuberculosis gyrase. H3D-005722 and related SPTs displayed high activity against gyrase and increased levels of enzyme-mediated double-stranded DNA breaks. The activities of these compounds were similar to those of the fluoroquinolones, moxifloxacin, and ciprofloxacin and greater than that of zoliflodacin, the most clinically advanced SPT. All the SPTs overcame the most common mutations in gyrase associated wit

SUBMITTER: Byl JAW 

PROVIDER: S-EPMC10006343 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature