Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3698-3703. doi: 10.1016/j.bmcl.2017.07.008. Epub 2017 Jul 5.

Abstract

A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.78μg/mL and along with no significant cytotoxicity against MBMDMQs (mouse bone marrow derived macrophages). Molecular docking of the target compounds into the active site of DprE1 (Decaprenylphosphoryl-β-d-ribose-2'-epimerase) enzyme revealed noteworthy information on the plausible binding interactions.

Keywords: 1,2,3-Triazoles; Antimycobacterial activity; Cytotoxicity; Molecular docking; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / antagonists & inhibitors
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / toxicity
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Bone Marrow Cells / cytology
  • Catalytic Domain
  • Click Chemistry
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Structure-Activity Relationship
  • Thermodynamics
  • Triazoles / chemistry*
  • Triazoles / pharmacology*
  • Triazoles / toxicity

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Triazoles
  • Alcohol Oxidoreductases
  • DprE1 protein, Mycobacterium tuberculosis