Mannich Ketones as Possible Antimycobacterial Agents

Arch Pharm (Weinheim). 2017 Sep;350(9). doi: 10.1002/ardp.201700102. Epub 2017 Jul 28.

Abstract

Twenty-three known unsaturated and fused Mannich ketones and their reduced derivatives (amino alcohols) were selected for an antituberculotic study. They were screened against several mycobacterial strains including Mycobacterium tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration values were also determined using the standard antituberculotic drug isoniazid (INH) as a reference. Structure-activity relationships were also studied. The mode of action of the test compounds was investigated using transmission electron microscopy, high-performance liquid chromatography, and matrix-assisted desorption/ionization mass spectrometry. Several test substances proved to be as potent as INH, but their antimycobacterial spectra were broader than that of INH. Our findings suggest that their mode of action is probably through the inhibition of mycobacterial cell wall biosynthesis.

Keywords: Atypical mycobacteria; Antimycobacterial activity; Antituberculosis activity.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / pharmacology
  • Isoniazid / pharmacology
  • Ketones / chemical synthesis*
  • Ketones / pharmacology*
  • Mannich Bases / chemical synthesis*
  • Mannich Bases / pharmacology*
  • Microbial Sensitivity Tests
  • Mycobacterium / drug effects*
  • Mycobacterium tuberculosis / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Ketones
  • Mannich Bases
  • Isoniazid