Primary discovery of 1-aryl-5-substituted-1H-1,2,3-triazole-4-carboxamides as promising antimicrobial agents

Abstract

Three series of novel 1H-1,2,3-triazole-4-carboxamides: 1-aryl-5-alkyl/aryl-1H-1,2,3-triazole-4-carboxamides, 1-aryl-5-amino-1H-1,2,3-triazole-4-carboxamides and 1,2,3-triazolo[1,5-a]quinazoline-3-carboxamides were synthesized via base-mediated click azide reactions. Compounds were evaluated for their antimicrobial activities against primary pathogens: Gram-positive and Gram-negative bacterial strains Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, as well as fungal strain Cryptococcus neoformans var. grubii and Candida albicans. Compounds exhibiting moderate to good activities were selected for SAR analysis. Several 5-methyl-1H-1,2,3-triazole-4-carboxamides 4d, 4l, 4r, showed potent antibacterial effect against S. aureus. On the contrary, 5-amino-1H-1,2,3-triazole-4-carboxamide 8b and [1,2,3]triazolo[1,5-a]quinazoline-3-carboxamide 9a were active against pathogenic yeast C. albicans. Thus, compound 4l under 1 µM demonstrated 50% growth inhibition against S. aureus. At the same concentration, the compound 9a killed approx. 40% of C. albicans cells. In general, these compounds demonstrated selective action and no significant impact on the viability of human keratinocytes of HaCaT line.