Understanding the antifungal activity of terbinafine analogues using quantitative structure-activity relationship (QSAR) models

Terbinafine and its analogues, which are a major class of non-azole antifun gal agents, are known to act by inhibition of squalene epoxidase enzyme in fungal cells. We have performed a quantitative structure-activity relations hip (QSAR) study on a series of 92 molecules using different types of physi cochemical descriptors. Inhibitors were divided into five classes depending upon chemical structure. QSAR models were generated for correlation betwee n antifungal activity against Candida albicans using genetic function appro ximation (GFA) technique. Equations were evaluated using internal as well a s external test set predictions. Models generated for all these classes sho w that steric properties and conformational rigidity of side chains play an important role for the activity. The present QSAR analysis agrees with the results of the previously reported CoMFA study. (C) 2000 Elsevier Science Ltd. All rights reserved.