Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents

Bioorg Med Chem Lett. 2019 Feb 15;29(4):539-543. doi: 10.1016/j.bmcl.2019.01.001. Epub 2019 Jan 3.

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 H37Rv(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, compound IIIa16 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.

Keywords: (E)-4-Oxo-2-crotonic acid derivatives; Antituberculosis agents; Drug-resistant-TB; Mycobacterium tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Crotonates / chemistry
  • Crotonates / pharmacology*
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Structure-Activity Relationship

Substances

  • Amides
  • Antitubercular Agents
  • Crotonates
  • crotonic acid