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

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-1Hpyrazol-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 mu g/mL. Compounds 7g, 7i, 7k, 7l and 7m were further evaluated for ergosterol inhibition assay against A. niger cells sample at 31.5 ugimL 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. (C) 2019 Elsevier Masson SAS. All rights reserved.