Rapid expansion of antimicrobial-resistant pathogens has intensified the demand for chemotypes that are both potent and environmentally sustainable. We describe a green one-pot strategy for constructing a small library of polyhydroquinoline derivatives (4a–4e) starting from 5-methyl-2-aminopyridine and aromatic aldehydes in ethanol under catalytic HCl. Antimicrobial activity was assessed by agar well diffusion against Staphylococcus aureus, Bacillus anthracis, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger. Lead compound 4a produced inhibition zones of 30–31 mm for Gram-positive, 27–28 mm for Gram-negative bacteria and 24–26 mm for fungal strains, closely matching or surpassing the reference drugs streptomycin and fluconazole. Further, SwissADME predicted full Lipinski compliance and high GI absorption, while AutoDock Vina gave strong binding to S. aureus and E. coli (4a: –11.9/–9.9 kcal mol⁻¹). These findings showed a promising broad-spectrum antimicrobial derived via a sustainable synthesis.
