Design of some β-lactam derivatives as prospective antibacterial agents: Synthesis, characterization, computational analysis, and molecular docking studies
Umme Aiman Liza, Sumaiya Khan, Md Aman Ullah Aman, Md Sarwar Hossen Sogib, Md Alamgir Hossain, Anamika Sultana, Mohammad Mamun HossainA series of substituted β-lactam derivatives (3a–e) were synthesized via Schiff base intermediates using a Staudinger [2+2] cycloaddition reaction and characterized by FT-IR and 1H NMR spectroscopy. DFT calculations (B3LYP/6-31G(d)) were performed to investigate molecular geometry, electronic properties, and reactivity descriptors. Conceptual DFT analysis revealed that compounds 3c, 3d, and 3e display high electrophilicity indices (ω = 5.84–5.99 eV), indicating strong electrophilic reactivity, while compound 3b shows the lowest electrophilicity (ω = 2.406 eV) and the largest energy gap, suggesting higher kinetic stability. Molecular electrostatic potential analysis identified key reactive sites responsible for intermolecular interactions. Molecular docking against Escherichia coli BepA metalloprotease (PDB: 6SAR) revealed good binding affinities (−7.2 to −8.1 kcal/mol), with compound 3d showing the strongest interaction. These results suggest that the synthesized β-lactam derivatives may serve as promising scaffolds for antibacterial drug development.