Synthesis and antimicrobial investigation of novel β-lactam derivatives

Background Antibacterial agents containing β-lactam derivatives have been widely used in medicine because of their broad-spectrum effectiveness against various infectious diseases. β-Lactam antibiotics remain one of the most important classes of antibacterial agents, and the development of new β-lactam derivatives continues to be essential for overcoming microbial resistance. Therefore, the discovery of novel β-lactam compounds remains an important area in medicinal chemistry for the development of improved antibacterial agents. Objective The present study aimed to synthesize new β-lactam derivatives derived from sulfapyridine Schiff bases and to evaluate their biological activity using laboratory investigations and molecular docking analysis. Methods Sulfapyridine-derived Schiff bases were prepared through condensation reactions with different aromatic aldehydes and used as key intermediates for the synthesis of β-lactam derivatives. The structures of the synthesized compounds were confirmed using FT-IR, 1 H-NMR, and 13 C-NMR spectroscopic techniques. Two series of β-lactam derivatives were synthesized. The first series [A5–A8] was obtained through the reaction of Schiff bases [A1–A4] with chloroacetyl chloride in the presence of triethylamine. The second series [A9–A12] was synthesized through cycloaddition reactions between the prepared Schiff bases and diclofenac acid in the presence of ρ-toluenesulfonyl chloride and trimethylamine. The synthesized compounds were biologically evaluated, and molecular docking studies were carried out against biologically relevant bacterial targets, including Escherichia coli (PDB ID: 2EG7) and Staphylococcus aureus (PDB ID: 2W9S). Results Molecular docking studies were performed to evaluate the antibacterial activity of compounds A5–A12 against Escherichia coli and Staphylococcus aureus. Several synthesized derivatives, particularly A7–A9 and A12, exhibited enhanced antibacterial activity compared with the reference drug. Experimental and theoretical findings suggested that β-lactam-based compounds may serve as promising scaffolds for the development of new antibacterial agents. Compared with amoxicillin (−7.5 kcal/mol), compounds A10 and A11 demonstrated lower binding energies (−9.0 and − 8.4 kcal/mol, respectively), indicating strong interactions with bacterial target proteins. Conclusion Molecular docking studies supported the experimental antibacterial findings and provided insight into possible ligand–protein interactions, confirming the biological potential of the synthesized β-lactam derivatives. These findings support the continued investigation of β-lactam scaffolds as promising candidates for future antibacterial drug development.