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Synthesis and Evaluation of Novel 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-phenylacetohydrazide as Potential Antimicrobial Agents

S Athul, S. Bhuvaneshwari, Avani Anu G., Prameela H C, Anu Rohit Melge, Aravind Madhavan, Bipin Gopalakrishnan Nair, Geetha B. Kumar et al.

International Journal of Molecular Sciences, 2025

Abstract

This study details the design, synthesis, and evaluation of a novel series of fourteen 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrid compounds. The primary objective was to investigate their potential as antimicrobial agents and assess their cytotoxicity. A systematic approach combining in silico screening and experimental validation was employed. The initial in silico analysis, using SwissADME, identified compounds with favorable drug-like properties. Subsequently, all fourteen compounds were synthesized and characterized using various spectroscopic methods. Their antibacterial efficacy was evaluated in vitro against Gram-negative (Klebsiella aerogenes) and Gram-positive (Enterococcus sp.) bacteria through growth kinetics and colony-forming unit (CFU) assays. Cytotoxicity was assessed using MTT assays on HEK (human embryonic kidney) cell lines. The compound, 2-((1H-1,2,4-triazol-3-yl)thio)-N′-(2-fluorobenzylidene)-N-phenylacetohydrazide emerged as the most promising candidate, demonstrating broad-spectrum antibacterial activity. These findings highlight the potential of 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrids as a scaffold for developing new antimicrobial agents. Furthermore, this study suggests possible environmental applications for these compounds in antimicrobial resistance (AMR) management.

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