Docking-based 3D-QSAR study for 11beta-HSD1 inhibitors.
11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes catalyze the conversion of biologically inactive 11-ketosteroids into their active 11beta-hydroxy derivatives and vice versa. 11beta-HSD1 has been studied as a potential treatment for metabolic disease such as diabetes and obesity. To find correlation between 11beta-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 11beta-HSD1 inhibitors.
Lee
Jin Hee
JH
Center for Drug Discovery Technologies, Korea Research Institute of Chemical Technology, Yu seong-gu, Daejon 305-600, Republic of Korea.
Kang
Nam Sook
NS
Yoo
Sung-Eun
SE
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D008024:Ligands; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1