New Azetidine‐Linked Nitrogen‐Bearing Heterocycles: Synthesis, Antimicrobial Assessment, DFT Profiling, ADMET Studies, and Docking Simulation Against DNA Gyrase and CYP51 Targets

ABSTRACT The rapid rise of antimicrobial resistance necessitates the development of new chemotypes with improved efficacy and drug‐like properties. In this study, 10 previously unexplored azetidine–pyridazine scaffolds were synthesized under mild, metal‐free conditions, and evaluated for their dual antibacterial and antifungal potential. Several derivatives displayed strong in vitro activity against Staphylococcus aureus , with five compounds outperforming chloramphenicol. Two compounds also exhibited twofold higher antifungal potency than griseofulvin against Candida albicans . All molecules demonstrated favourable ADMET characteristics, including high predicted gastrointestinal absorption, no violations of drug‐likeness rules, and non‐substrate behaviour toward P‐glycoprotein. DFT‐based electronic analysis and molecular docking against DNA gyrase (5MMN) and CYP51 (3JUV) provided molecular‐level justification for the observed SAR and antimicrobial effects. Overall, the combination of green synthesis, potent bioactivity, desirable pharmacokinetics, and strong target interactions highlights azetidine–pyridazine scaffolds as promising leads for future antimicrobial drug development.