Abstract

3D- QSAR OF N- SUBSTITUTED IMIDAZOLES AS ANTIFUNGAL AGENTS

Vithal M. Kulkarni*, Sandeep S. Pathare and Kakasaheb R. Mahadik

Abstract

Azole antifungals are widely studied using various methods of drug design. A series of N-substituted imidazole derivatives was examined to determine the structural requirements for antifungal activity by three-dimensional quantitative structure-activity relationship (3DQSAR) using comparative molecular field analysis (CoMFA). A training set of 50 compounds was used to establish the CoMFA model, which was validated by evaluation of a test set of 15 compounds. In this study, the superimposition of molecules was carried out by atombased fit (rms), multi fit and field fit. The best QSAR model was obtained from rms fit with cross-validated r2 = 0.725, conventional r2 = 0.939 and predictive r2 = 0.518. This series of compounds was also analyzed by genetic function approximation (GFA). The best model with cross-validated r2 of 0.608 and predictive r2 of 0.391 emphasized the importance of molecular shape analysis parameters. The models obtained from the present study may be useful for the development of new imidazole derivatives as potential antifungals.

Keywords: QSAR, CoMFA, Antifungal activity, N-substituted Imidazole derivatives.