AntimicrobialEfficacy of 1,2,3-Triazole-IncorporatedIndole-Pyrazolone against Drug-Resistant ESKAPE Pathogens: Designand Synthesis

In the current study, we report the synthesis of novel 4-((1-((1<i>H</i>-1,2,3-triazole-4-yl)methyl)-1<i>H</i>-indol-3-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3<i>H</i>-pyrazole-3-one derivatives <b>5a</b>–<b>o</b>. 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 <b>5e</b>, <b>5h</b>, and <b>5i</b> displayed potent activity with MIC value <b>10 μg/mL</b> against Acinetobacter baumannii, in comparison to standard drugs chloramphenicol and ampicillin. Compounds <b>5d</b>, <b>5h</b>, <b>5i</b>, <b>5l</b>, <b>5m,</b> and <b>5n</b> 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 <b>5a</b>–<b>o</b> exhibit no significant cytotoxicity at concentrations up to <b>100 μg/mL</b>, 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.