Docking-based 3D-QSAR study for 11β-HSD1 inhibitors

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) enzymes catalyze the conversion of biologically inactive 11-ketosteroids into their active 11 beta-hydroxy derivatives and vice versa. 11 beta-HSD1 has been studied as a potential treatment for metabolic disease such as diabetes and obesity. To find correlation between 11 beta-HSD1 and inhibitors, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 70 inhibitors, based on molecular docking conformations obtained by using FlexX-Pharm. The studies include comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Based on the docking results, highly predictive 3D-QSAR models were developed with q(2) values of 0.543 and 0.519 for CoMFA and CoMSIA, respectively. A comparison of the 3D-QSAR field contributions with the structural features of the binding site showed good correlation between the two analyses. Therefore, these results should be useful to the prediction of the activities of new 11 beta-HSD1 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.