Uygun Cebeci, YıldızKeşkek Karabulut, YaseminCeylan, Şule2026-07-062026-07-06202510703632https://hdl.handle.net/11494/6256Abstract: The emergence of antimicrobial resistance (AMR) poses a critical threat to global health, underscoring the need for new antimicrobial agents. In this study, a novel series of 1,2,4-triazole derivatives was synthesized from methylpiperazine intermediates via esterification, hydrazide formation, thiourea condensation, and Mannich-type reactions. Structural characterization was performed using FT-IR, 1H, 13C NMR, and EI-MS techniques. Antimicrobial activities of the synthesized compounds were evaluated via broth microdilution. One derivative displayed remarkable broad-spectrum activity with MIC values <0.24 µg/mL against E. coli, S. aureus, M. smegmatis, and C. albicans. Molecular docking against E. coli DNA gyrase B (PDB: 4PRV) revealed strong binding affinities for two derivatives (–9.9 and –9.8 kcal/mol), correlating well with in vitro results. Key interactions included hydrogen bonding, π–π stacking, and halogen bonding. SAR analysis emphasized the role of electron-withdrawing and hydrophobic groups in enhancing activity. These triazole derivatives show promise as potent antimicrobial candidates targeting DNA gyrase B.eninfo:eu-repo/semantics/openAccess124-triazoleAntimicrobial activityDNA gyrase B inhibitionMethylpiperazineMolecular dockingStructure–activity relationship (SAR)Article95102900291010.1134/S10703632256028202-s2.0-105020758225Q3WOS:001606918900013Q4