Docking and Ultrasonic Synthesis of Schiff Base and Azo-Heterocyclic Compounds Derived from N-Aminophthalimide: Antibacterial Evaluation

Abstract

In this study, a series of Schiff base derivatives derived from N-aminophthalimide were successfully synthesized through green chemistry protocols using ultrasonic techniques. The prepared compounds were further cyclized with chloroacetyl chloride and ethyl thioglycolate to obtain novel heterocyclic nitrogen-containing structures. The chemical structures of the synthesized compounds were confirmed via spectroscopic analyses, including FT-IR, ¹H-NMR, and ¹³C-NMR techniques. Molecular docking studies were conducted using Discovery Studio 2024 to assess the interaction of the synthesized compounds with Coagulation Factor X (PDB ID: 1FJS). Among the evaluated compounds, S2 exhibited the most promising binding affinity, with a docking score of –10.4 kcal/mol, indicating strong interaction with the active site through multiple hydrogen bonds. Other compounds showed docking scores ranging between –7.7 and –9.3 kcal/mol. The antibacterial activities of the selected compounds were evaluated against Gram-negative and Gram-positive bacteria. The inhibitory zone diameters reached up to 19 mm for Klebsiella spp. (A1) and 17 mm for Staphylococcus aureus (A1). In contrast, several compounds exhibited moderate activity against Escherichia coli, with inhibition zones ranging from 10 to 12 mm. In conclusion, the synthesized compounds demonstrated significant potential as antibacterial agents and exhibited strong binding affinity towards Coagulation Factor X, suggesting their possible pharmaceutical applications.