2D QSAR studies on a series of bifonazole derivatives with antifungal activity

Abstract

Candida albicans (CA) has been identified as the major opportunistic pathogen in immunosuppressed patients. Most of currently available drugs are either highly toxic or becoming ineffective against resistant strains. An approach to overcome this burden relies on azole derivatives with increased potency and selectivity. Aiming at shedding some light on structural and chemical features that are important for the antifungal activity of azole derivatives, classical 2D QSAR and hologram QSAR (HQSAR) studies were performed for a diverse set of 52 bifonazole derivatives with antifungal activity. Topological descriptors, employed in Classical QSAR studies, resulted in models with low correlation (r2 = 0.38, q2 = 0.27) and lack of predictive power (r2pred = -0.6). On the other hand molecular holograms afforded HQSAR models with good correlation coefficients (r2 = 0.92, q2 = 0.65) and good predictive ability (r2pred = 0.79). ©2009 Sociedade Brasileira de Química.