Green and One Pot Generation of Schiff Bases and Studies of Their Biological Potential

The ongoing challenge of antimicrobial resistance necessitates the development of novel, potent, and environmentally sustainable therapeutic agents. In this study, a green and efficient one-pot synthesis protocol was employed for the generation of a series of Schiff base derivatives (compounds 1-8) using a phosphorus pentoxide/alumina (P₂O₅/Al₂O₃) catalyst under solvent-free or benign solvent conditions. Their antimicrobial potential was evaluated via in vitro assays against two Gram-positive bacteria (Staphylococcus aureus, Bacillus anthracis), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and two fungal strains (Candida albicans, Aspergillus niger) using the cup-plate method. Compound 8 exhibited the highest antibacterial and antifungal activity, with inhibition zones comparable to standard drugs streptomycin and fluconazole. In silico ADME profiling using Swiss ADME confirmed drug-likeness for all compounds, with most showing high gastrointestinal absorption and compliance with Lipinski’s rule of five. Molecular docking studies were conducted against S. aureus (PDB ID: 1JIJ) and E. coli (PDB ID: 1KZN), revealing strong binding affinities for several compounds, particularly compound 8, which showed the most favourable interactions. These results underscore the potential of Schiff base scaffolds, with environmentally friendly synthesis approach aligning with green chemistry principles, offering a viable route for sustainable drug development.