Design, synthesis and evaluation of oxime-functionalized nitrofuranylamides as novel antitubercular agents

A series of novel oxime-functionalized nitrofuranylamides were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against MTB H37Rv and drug-resistant clinical isolates. Among them, two compounds 7a and 7b which were comparable to the first-line anti-TB agents INH and RIF against MTB H37Rv, also demonstrated great potency against drug-resistant clinical isolates, suggesting they may serve as new and promising candidates for further anti-TB drug discovery. [Display omitted] •All oxime-functionalized nitrofuranylamides showed considerable activity against the tested MTB strains.•Targets 7a and 7b were far more potent than INH and RIF against drug-resistant clinical isolates.•The SAR was enriched. A series of oxime-functionalized nitrofuranylamides were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against MTB H37Rv and drug-resistant clinical isolates. Among them, two compounds 7a and 7b exhibited excellent activity against the three tested strains. Both of them were comparable to the first-line anti-TB agents INH and RIF against MTB H37Rv, and were far more potent than INH and RIF against MDR-TB 16833 and 16995 strains. Thus, both of them could act as leads for further optimization.