A Facile and Efficient Approach for the Synthesis of Novel 2-Azetidinone Derivatives and Their Biological Activities

Abstract

Background: Substituted 2-azetidinones are of interest as β-lactam frameworks for synthetic and antibacterial investigations. Aim: This study examined the synthesis, characterisation, antibacterial responses and predicted protein interactions of eight derivatives. Methods: Schiff bases prepared from aromatic aldehydes and aromatic amines were cyclised using ketene obtained from acetyl chloride in the presence of triethylamine. The products, designated B1–B8, were purified, and spectroscopic data were reported using FT-IR and nuclear magnetic resonance techniques. Antibacterial responses were examined at concentrations of 1.0, 2.0 and 3.0 mg/mL against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Molecular docking against penicillin-binding protein 3 (PBP3; PDB ID: 8C5W) was undertaken using AutoDock Vina. Results: Inhibition-zone diameters varied across compounds and concentrations, with several derivatives showing larger zones at higher concentrations. At 3.0 mg/mL, B2, B4 and B5 each produced 24 mm zones against E. coli; B2 produced a 25 mm zone against S. aureus; and B8 produced a 24 mm zone against P. aeruginosa. B2 showed the most negative reported docking score (−5.943 kcal/mol), while B7 yielded positive scores. Docking-box centres differed among compounds, limiting direct comparisons. Conclusions: The findings describe the preparation of eight derivatives and preliminary antibacterial responses. Standardised docking, reconciliation of the reported analytical data, and additional quantitative biological testing are required to clarify the relative activities and possible mechanisms of these derivatives.