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

• Published in: Bioorganic & medicinal chemistry letters 2018-10, Vol.28 (18), p.3064-3066
• Main Authors: Fan, Yi-Lei, Wu, Jian-Bing, Ke, Xing, Huang, Zhong-Ping
• Format: Article
• Language: English
• Subjects: Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; Anti-mycobacterial; Anti-tubercular; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Dose-Response Relationship, Drug; Drug Design; Microbial Sensitivity Tests; Molecular Structure; Multi-drug resistant; Mycobacterium tuberculosis - drug effects; Nitro Compounds - chemical synthesis; Nitro Compounds - chemistry; Nitro Compounds - pharmacology; Nitrofuran; Nitrofuranylamides; Oxime; Oximes - chemistry; Oximes - pharmacology; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.07.046

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.