Lipophilicity Driven QSAR Models For Antimicrobial Azaphenanthrene Scaffolds

Abstract

Nitrogen-fused polycyclic aromatic heterocycles, particularly azaphenanthrenes, represent versatile scaffolds in medicinal chemistry owing to their enhanced electron distribution, hydrogen-bonding capacity, and metabolic stability. This study reports the synthesis and antimicrobial evaluation of azaphenanthrene derivatives bearing diverse substituents, alongside quantitative structure-activity relationship (QSAR) modeling to elucidate structure-activity trends. Compounds exhibited potent activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas diminuta, often surpassing ampicillin, with lipophilicity (log P) emerging as the primary correlate of potency (r = 0.86–0.96)