title: CoMFA and CoMSIA analysis of 2,4-thiazolidinediones derivatives as aldose reductase inhibitors.
abstract: Diabetes remains a life-threatening disease. The clinical profile of diabetic subjects is often worsened by the presence of several long-term complications, for example neuropathy, nephropathy, retinopathy, and cataract. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 2,4-thiazolidinediones derivatives as aldose reductase (ALR2) inhibitors. Molecular ligand superimposition on a template structure was finished by the database alignment method. The 3D-QSAR models resulted from 44 molecules gave q (2) values of 0.773 and 0.817, r (2) values of 0.981 and 0.979 for CoMFA and CoMSIA, respectively. The contour maps from the models indicated that a large volume group next to the R-substituent will increase the ALR2 inhibitory activity. In fact, adding a -CH(2)COOH substituent at the R-position would generate a new compound with higher predicted activity.
authors.affiliation: Department of Material and Chemical Engineering, Guilin University of Technology, 541004 Guilin, People's Republic of China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Shu-Shen
authors.initials: SS
authors.lastname: Liu
authors.forename: Li-Tang
authors.initials: LT
authors.lastname: Qin
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Mo
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000465:Algorithms; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D000449:Aldehyde Reductase