Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents. Issue 4 (15th February 2019)

• Record Type: Journal Article
• Authors: Ren, Jinfeng; Xu, Jian; Zhang, Guoning; Xu, Changliang; Zhao, LiLi; You, XueFu; Wang, Yucheng; Lu, Yu; Yu, Liyan; Wang, Juxian
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 4(2019)
• Page Start: 539
• Page End: 543
• Publication Date: 2019-02-15
• Subjects: Mycobacterium tuberculosis -- Antituberculosis agents -- (E)-4-Oxo-2-crotonic acid derivatives -- Drug-resistant-TB; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.01.001
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A series of novel (E) -4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents and evaluated for their biological activity. Our results reveal that compoundIIIa16 was found to have the best activity with MIC of 0.125 μg/mL against MTB and with MIC in the range of 0.05–0.48 µg/mL against drug-resistant clinical MTB isolates. Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Highlights: Novel (E) -4-oxo-crotonamide derivatives containing different substituents were designed and synthesized. The SAR were summarized for further antitubercular drug discovery. CompoundIIIa16 exhibit potent MIC values against MTB H37 Rv and some MDR-MTB strains. Abstract: A series of novel (E) -4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37 Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against MTB with MIC ranging from 0.125 to 4 µg/mL. Especially, compoundIIIa16 was found to have the best activity with MIC of 0.125 μg/mL against MTB and with MIC in the range of 0.05–0.48 µg/mL against drug-resistant clinical MTB isolates.