Antibacterial Activity of Microwave-Synthesized Isoxazole Derivatives: In vitro and In silico Insights

An easy and efficient procedure was developed for the synthesis of isoxazole derivatives in good to excellent yields (53–85%) via the reaction of substituted β-chloroacrylonitrile under classical and microwave conditions. The synthesized compounds were evaluated in vitro and in silico for their antibacterial activity against E. coli, B. subtilis, S. aureus, and P. aeruginosa. Antibacterial screening revealed that compound 3a exhibited the strongest inhibition against E. coli and B. subtilis (MICs 12.5 and 25 μg/mL, respectively), while compound 3c showed the highest activity against P. aeruginosa (MIC 50-100 μg/mL). Molecular docking studies confirmed these results, showing more favorable binding energies (–8.4 to –9.0 kcal/mol for compounds 3a–3c) compared to gentamicin (–5.0 to –6.4 kcal/mol). The docking targets included β-lactamase (1BTL), penicillin-binding protein (1DQ9), tyrosyl-tRNA synthetase (8H1B), and outer membrane protein OprM (2UV0). This combined in vitro and in silico evaluation has highlighted compounds 3a, 3b, and 3c as the most promising antibacterial agents, with strong binding affinities and significant inhibitory effects against pathogenic bacteria.