Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents.
Li L, Lv K, Yang Y, Sun J, Tao Z, Wang A, Wang B, Wang H, Geng Y, Liu M, Guo H, Lu Y.
A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC < 0.016-0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.