Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as New Antitubercular Agents with Potent In Vitro and In Vivo Efficacy

Molecules. 2019 May 27;24(10):2021. doi: 10.3390/molecules24102021.

Abstract

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.

Keywords: (3-benzyl-5-hydroxyphenyl)carbamate; Mycobacterium tuberculosis; antitubercular activity.

MeSH terms

  • A549 Cells
  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Carbamates / chemistry
  • Carbamates / pharmacology*
  • Cell Death / drug effects
  • Disease Models, Animal
  • Drug Discovery*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Treatment Outcome
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Carbamates