Chemical synthesis and biological evaluation of triazole derivatives as inhibitors of InhA and antituberculosis agents

Eur J Med Chem. 2012 Jun:52:275-83. doi: 10.1016/j.ejmech.2012.03.029. Epub 2012 Mar 23.

Abstract

A series of triazoles have been prepared and evaluated as inhibitors of InhA as well as inhibitors of Mycobacterium tuberculosis H(37)R(v). Several of these new compounds possess a good activity against InhA, particularly compounds 17 and 18 for which molecular docking has been performed. Concerning their activities against M. tuberculosis H(37)R(V) strain, two of them, 3 and 12, were found to be good inhibitors with MIC values of 0.50 and 0.25 μg/mL, respectively. Particularly, compound 12 presenting the best MIC value of all compounds tested (0.6 μM) is totally inactive against InhA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology*
  • Oxidoreductases / antagonists & inhibitors*
  • Oxidoreductases / chemistry
  • Protein Conformation
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Triazoles
  • Oxidoreductases
  • InhA protein, Mycobacterium