Spiropyrimidinetrione DNA Gyrase Inhibitors with Potent and Selective Antituberculosis Activity.

ABSTRACT: New antibiotics with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new spiropyrimidinetriones (SPTs), DNA gyrase inhibitors having activity against drug-resistant Mycobacterium tuberculosis (Mtb), the causative agent of TB. While the clinical candidate zoliflodacin has progressed to phase 3 trials for the treatment of gonorrhea, compounds herein demonstrated higher inhibitory potency against Mtb DNA gyrase (e.g., compound 42 with IC₅₀ = 2.0) and lower Mtb minimum inhibitor concentrations (0.49 μM for 42). Notably, 42 and analogues showed selective Mtb activity relative to representative Gram-positive and Gr

SUBMITTER: Govender P 

PROVIDER: S-EPMC9233935 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature