THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF FARNESYL PROTEIN TRANSFERASE INHIBITORS

AIM To build a three dimensional structure model that correlates the biological activities and the structures of a series of farnesyl protein transferase (FPT) inhibitors exemplified by the compound of 2,3,4,5 tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(2-biphenylylcarbonyl)-1H-1,4-benzodiazepine. METHODS AND RESULTS Thirty-two FPT inhibitors with two types of scaffold were analyzed. Active conformations of which were studied using system search, a 3D-QSAR model were constructed using the method of comparative molecular field analysis (CoMFA). The resulting of cross validated R²_CV=0.602, non-cross-validated R²=0.958, SE=0.270 and F=124.5 indicate that the 3D-model possesses an ability to predict activities of new inhibitors. CONCLUSION The information of CoMFA model offers an approach to designing new FPT inhibitors.