Synthesis and antimicrobial investigation of novel β-lactam derivatives

<ns3:p> Background β-Lactam derivatives are widely studied due to their proven pharmacological benefits and capacity to suppress a wide range of microbiological infections. These compounds represent an important class of antibacterial agents, and continued structural modification of β-lactams remains essential to overcome antimicrobial resistance. The synthesis of new β-lactam scaffolds is therefore a key strategy in medicinal chemistry for the development of more effective antibacterial drugs. Objective The present study aimed to synthesize new β-lactam derivatives based on sulfapyridine Schiff bases and to evaluate their potential biological activity using experimental characterization and molecular docking analysis. Methods Sulfapyridine-based Schiff bases were prepared through condensation reactions and used as key intermediates for the synthesis of β-lactam derivatives. The synthesized compounds were confirmed using spectroscopic techniques, including FT-IR, <ns3:sup>1</ns3:sup> H-NMR, and <ns3:sup>13</ns3:sup> C-NMR. In this study, two types of β-lactam derivatives were synthesized. Condensation of the sulfanilamide drug with selected aromatic aldehydes in the presence of glacial acetic acid gives the corresponding Schiff bases [A1-A4]. The reaction of prepared Schiff bases with chloro acetyl chloride in the presence of triethylamine gave the first type of β-lactam derivatives [A5-A8]. The second type of β-lactam derivatives [A9-A12] were synthesized via cycloaddition between prepared Schiff bases with diclofenac acid in the presence of ρ-toluene sulfonyl chloride and trimethylamine. Biological activity was evaluated, and molecular docking studies were performed against the target protein (PDB ID: 1EA1). Results Several synthesized derivatives, including A7, A8, A9, and A12, demonstrated enhanced antibacterial activity and outperformed reference medications. Experimental and theoretical data indicated that β-lactam compounds represent viable scaffolds for the development of novel antibacterial agents. Compared to the reference drug amoxicillin (−7.5 kcal/mol), compounds A10 and A11 exhibited the lowest binding energies (−9.0 and −8.4 kcal/mol, respectively), suggesting strong interaction with the target protein. Conclusion The agreement between in vivo biological results and in silico molecular docking data supports the potential biological activity of the synthesized β-lactam derivatives. These findings highlight the importance of β-lactam scaffolds as promising candidates for future antibacterial drug development. </ns3:p>