Morpholine Conjugated Imidazole Schiff Bases: Synthesis, Antimicrobial Profiling, and Computational Insights

Abstract

Heterocyclic medication modification has augmented disease prevention by improving its pharmacodynamic and pharmacokinetic properties. In response to the current interest in the antimicrobial properties of morpholine‐conjugated imidazole Schiff base derivatives ( 7a–7j ), have been synthesized using acetic acid in the presence of a green solvent. A three‐step reaction has been carried out to get the desired molecules. This method can tolerate a variety of electron‐rich and electron‐deficient functionalities, such as methyl, chloro, fluoro, bromo, and nitro, to produce the corresponding derivatives. The structures of the compounds were validated using FTIR, 1 H NMR, and HRMS spectrum analysis. In order to establish the biological activity of the compounds against Gram‐positive bacteria ( Staphylococcus aureus and Bacillus subtilis ), two Gram‐negative bacteria ( Salmonella typhi and Pseudomonas aeruginosa ), and two fungal strains ( Aspergillus flavus and Aspergillus niger ), the broth microdilution method was used. Excellent in vitro activity was demonstrated by compounds bearing bromo and fluoro substituents. Compound 7e exhibited significant antimicrobial action against all strains. The molecular docking results also support these findings through effective interaction with dihydrofolate reductase. Additionally, the in silico physicochemical assessment demonstrated a balanced ADME profile of compounds 7a–7f and 7j .