Design, synthesis, and antitubercular activity of 3-amidophenols with 5-heteroatomic substitutions

Arch Pharm (Weinheim). 2019 Apr;352(4):e1800277. doi: 10.1002/ardp.201800277. Epub 2019 Jan 30.

Abstract

A series of novel 3-amidophenols with 5-heteroatomic substitutions were designed and synthesized. Several compounds showed potent antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC = 0.25-5 μg/mL). Compounds 12j and 14i also displayed good inhibitory activity against M. tuberculosis H37Rv and two clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.39-3.12 μg/mL). The privileged compound 14i showed certain oral efficacy on a mouse infection model. The compounds are non-cytotoxic against L-O2 hepatocytes and RAW264.7 macrophagocytes. They did not exert inhibitory activity against representative Gram-positive and Gram-negative bacteria.

Keywords: 3-amidophenol derivative; Mycobacterium tuberculosis; antitubercular activity.

MeSH terms

  • Administration, Oral
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • RAW 264.7 Cells
  • Structure-Activity Relationship
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology

Substances

  • Amides
  • Antitubercular Agents
  • Phenols