Antioxidant and antibacterial activities of 5-mercapto(substitutedthio)-4-substituted-1,2,4-triazol based on nalidixic acid: A comprehensive study on its synthesis, characterization, and In silico evaluation

This study introduces a series of novel Alkyl thio-1,2,4-triazole (4a-p) and mercapto-1,2,4-triazole (3a-d) compounds derived from nalidixic acid. The synthesis was streamlined, involving interactions between nalidixic acid hydrazide and various isothiocyanates to yield cyclic and alkyl(aryl) sulfide compounds, characterized using 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant capabilities were quantified through DPPH and ABTS assays, highlighting significant potential, especially for compound 3d, which demonstrated an ABTS IC50 value of 0.397 μM, on par with ascorbic acid (IC50 = 0.87 μM). Antibacterial efficacy was established through MIC assessments against a broad spectrum of Gram-positive and Gram-negative bacteria, including Candida albicans. Compounds 3b, 4e, 4h, 4j, 4i, 4m, and 4o showed broad-spectrum activity, with 4k and 4m exhibiting pronounced potency against E. coli. Molecular docking studies validated the antibacterial potential, with compounds 4f and 4h showing high binding affinities (docking scores of −9.8 and −9.6 kcal/mol, respectively), indicating robust interactions with the bacterial enzyme targets. These scores underscore the compounds' mechanistic basis for their antibacterial action and support their therapeutic promise. Furthermore, compounds 3b, 4i, and 4m, identified through drug-likeness and toxicity predictions, were highlighted for their favorable profiles, suggesting their suitability for oral antibiotic therapies. This comprehensive study, blending synthetic, in vitro, and in silico approaches, emphasizes the triazole derivatives' potential as future candidates for antibiotic and antioxidant applications, particularly spotlighting compounds 3b, 4i, and 4m due to their promising efficacy and safety profiles.