Synthesis and evaluation of novel fluorinated pyrazolo-1,2,3-triazole hybrids as antimycobacterial agents

Bioorg Med Chem Lett. 2015 Aug 1;25(15):2918-22. doi: 10.1016/j.bmcl.2015.05.044. Epub 2015 May 27.

Abstract

A library of novel 3-trifluoromethyl pyrazolo-1,2,3-triazole hybrids (5-7) were accomplished starting from 5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-amine (1) via key intermediate 2-azido-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acetamide (3) through click chemistry approach. Thus obtained compounds in 5-7 series were evaluated for in vitro antimycobacterial activity against Mycobacterium smegmatis (MC(2) 155) and also verified the cytotoxicity. These studies engendered promising lead compounds 5q, 7b and 7c with MIC (μg/mL) values 15.34, 16.18 and 16.60, respectively. Amongst these three compounds, 2-(4-(4-methoxybenzoyl)-1H-1,2,3-triazol-1-yl)-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) acetamide (5q) emerged as the most promising antitubercular agent with lowest cytotoxicity against the A549 cancer cell line. This is the first report to demonstrate the pyrazolo triazole hybrids as potential antimycobacterial agents.

Keywords: 3-Trifluoromethyl pyrazolo-1,2,3-triazole hybrids; Antimycobacterial activity; Click chemistry; Cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line, Tumor
  • Click Chemistry
  • Halogenation
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mycobacterium Infections, Nontuberculous / drug therapy
  • Mycobacterium smegmatis / drug effects*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Pyrazoles
  • Triazoles
  • pyrazole