Efficient Synthesis, Structural Characterization, Antibacterial Assessment, ADME-Tox Analysis, Molecular Docking and Molecular Dynamics Simulations of New Functionalized Isoxazoles

This work describes the synthesis, characterization, and in vitro and in silico evaluation of the biological activity of new functionalized isoxazole derivatives. The structures of all new compounds were analyzed by IR and NMR spectroscopy. The structures of and were further confirmed by single crystal X-ray and their compositions unambiguously determined by mass spectrometry (MS). The antibacterial effect of the isoxazoles was assessed in vitro against , and bacterial strains. Isoxazole showed significant activity against and compared to the reference antibiotic drugs while and also exhibited some antibacterial effects. The molecular docking results indicate that the synthesized compounds exhibit strong interactions with the target proteins. Specifically, displayed a better affinity for , , and in comparison to the reference drugs. The molecular dynamics simulations performed on strongly support the stability of the ligand-receptor complex when interacting with the active sites of proteins from , , and . Lastly, the results of the Absorption, Distribution, Metabolism, Excretion and Toxicity Analysis (ADME-Tox) reveal that the molecules have promising pharmacokinetic properties, suggesting favorable druglike properties and potential therapeutic agents.