Design, synthesis, and biological evaluation of Schiff-Base Isoxazole hybrids: Exploring novel antimicrobial agents.

The rise of antimicrobial resistance necessitates the development of novel therapeutic agents. This study presents the design, in silico studies, synthesis, and biological evaluation of Schiff-base isoxazole hybrids as potential antimicrobial agents. Computational approaches, including molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and ADMET predictions, guided the design and assessment of these compounds. DFT analysis identified compound A20 (-0.0919 Hartree) as having the lowest energy gap, suggesting high reactivity. Molecular docking revealed strong binding affinities (-11.3 to -7.00 kcal/mol) comparable to standard antimicrobial drugs, while MD simulations confirmed the stability of protein-ligand interactions. ADMET analysis predicted favorable pharmacokinetic properties. Biological evaluations revealed promising antimicrobial potential of the synthesized compounds. A20 showed significant antifungal activity (MIC: 64 μg/mL), while A7 exhibited notable antibacterial activity (MIC: 1024 μg/mL). Further A20 in combination with standard antifungal drug fluconazole is exhibiting outstanding antifungal potential. Leading towards the possibility of developing a new drug against resistant microbial strains through combination therapy.