Nanoenabling MbtI Inhibitors for Next-Generation Tuberculosis Therapy

Le résumé fourni par la source

High Resolution Image Download MS PowerPoint Slide 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 (IC 50 = 11.2 μM) and a promising in vitro antitubercular activity (MIC 99 = 32 μM against M. bovis BCG). Esters of 1e were effectively loaded into poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes (POs) and delivered to intracellular mycobacteria, resulting in reduced Mtb viability. This study provides a foundation for the use of POs in the development of future MbtI-targeted therapies for tuberculosis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.