Antimicrobial Efficacy of 1,2,3-Triazole-Incorporated Indole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Design and Synthesis

Abstract

In the current study, we report the synthesis of novel 4-((1-((1H-1,2,3-triazole-4-yl)methyl)-1H-indol-3-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazole-3-one derivatives 5a–o. The compounds were prepared through a Knoevenagel condensation reaction and copper-catalyzed azide–alkyne cycloaddition (CuAAC) Click chemistry approach. The synthesized compounds exhibited promising antimicrobial activity against both Gram-positive and Gram-negative bacteria. Compounds 5e, 5h, and 5i displayed potent activity with MIC value 10 μg/mL against Acinetobacter baumannii, in comparison to standard drugs chloramphenicol and ampicillin. Compounds 5d, 5h, 5i, 5l, 5m, and 5n exhibited good-to-moderate antifungal activity against Candida albicans and Aspergillus niger equivalent to standard drugs nystatin and fluconazole. In this study, the cytotoxicity profile of a series of compounds was assessed using SHSY-5Y cells. The results indicate that compounds 5a–o exhibit no significant cytotoxicity at concentrations up to 100 μg/mL, in comparison to both untreated and vehicle control groups. These findings highlight the safety and tolerability of compounds as well as the potential of the synthesized compounds as effective agents against bacterial and fungal infections.