Nanoenabling MbtI Inhibitors for Next-Generation Tuberculosis Therapy.

ABSTRACT: The urgent need for safer and innovative antitubercular agents remains a priority for the scientific community. In pursuit of this goal, we designed and evaluated novel 5-phenylfuran-2-carboxylic acid derivatives targeting Mycobacterium tuberculosis (Mtb) salicylate synthase (MbtI), a key enzyme, absent in humans, that plays a crucial role in Mtb virulence. Several potent MbtI inhibitors demonstrating significant antitubercular activity and a favorable safety profile were identified. Structure-guided optimization yielded 5-(3-cyano-5-isobutoxyphenyl)furan-2-carboxylic acid (1e), which exhibited strong MbtI inhibition (IC₅₀ = 11.2 μM) and a promising in vitro antitubercular activity (MIC₉₉ = 32 μM against M. bovis BCG). Esters

SUBMITTER: Cazzaniga G 

PROVIDER: S-EPMC11912484 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature