Abstract
Abstract A set of 68 imidazole and cyanophenyl containing farnesyltransferase (FTase) inhibitors were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and a pharmacophore building method, the Catalyst program. The structures of these inhibitors were generated theoretically, and the conformations used in the 3D-QSAR studies were defined by docking them into the known structure of FTase binding pocket through GOLD3.1. The models constructed by CoMFA and CoMSIA were found to be conformed to each other and were both fitted in with the property potential surface of FTase active site. These pharmacophore features were also compared with those obtained by the Catalyst program and superimposed on the receptor site of FTase. All of the pharmacophore features are in well agreement with structural characteristics and in accord with each other. In addition, we provided a consensus between CoMSIA and Catalyst help improved the statistical results. The final 3D-QSAR models and the information of the inhibitor–receptor interaction would be guide the design of new drug leads against FTase activity.