Synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents

Eur J Med Chem. 2019 Oct 1;179:649-659. doi: 10.1016/j.ejmech.2019.06.074. Epub 2019 Jun 27.

Abstract

A series of 1-substituted benzyl-4-[1-phenyl-3-(4-methyl-2-aryl-1,3-thiazol-5-yl)-1H-pyrazol-4-yl]-1H-1,2,3-triazole derivatives (7a-y) have been synthesized by click reaction of 5-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)-4-methyl-2-aryl-1,3-thiazole (5a-e) with substituted benzyl azide. The starting compounds 5-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)-4-methyl-2-aryl-1,3-thiazole (5a-e) were synthesized from corresponding 3-(4-methyl-2-aryl-1,3-thiazol-5-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a-e) by using Ohira-Bestmann reagent. All newly synthesized thiazolyl-pyrazolyl-1,2,3-triazole derivatives were screened for antibacterial activity against two Gram negative strains, Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), a Gram positive strain Staphylococcus albus (NCIM 2178) and in vitro antifungal activity against Candida albicans (NCIM 3100), Aspergillus niger (ATCC 504) and Rhodotorula glutinis (NCIM 3168). Ten thiazolyl-pyrazolyl-1,2,3-triazole derivatives, 7b, 7g, 7i, 7j, 7k, 7l, 7m, 7n, 7p and 7v exhibited promising antifungal activity against A. niger with MIC 31.5 μg/mL. Compounds 7g, 7i, 7k, 7l and 7m were further evaluated for ergosterol inhibition assay against A. niger cells sample at 31.5 μg/mL concentration. The analysis of sterol inhibition assay revealed that ergosterol biosynthesis is decreased in the fungal samples treated with azole derivatives. Promising antifungal activity suggested that, these compounds could be further promoted for optimization and development which could have the potential to treat against fungal infection.

Keywords: 1,2,3-Triazole; Antibacterial activity; Antifungal activity; Ohira-bestmann reagent; Pyrazole; Thiazole.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Aspergillus niger / drug effects
  • Candida albicans / drug effects
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Proteus mirabilis / drug effects
  • Rhodotorula / drug effects
  • Staphylococcus / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents