title: Quantitative structure-activity analysis of 5-arylidene-2,4-thiazolidinediones as aldose reductase inhibitors.
abstract: Design of aldose reductase (ALR2) inhibitors has received considerable attention. Aldose reductase inhibitors, when administered from the onset of hyperglycemia, prevent the progression of polyol accumulation-linked complications. The feasibility that inhibition of aldose reductase provides a pharmacologically direct treatment for diabetic complications that is independent of the control of blood sugar levels has spurred the development of structurally diverse aldose reductase inhibitors. In this work, we report quantitative structure-activity relationship (QSAR) analysis performed by 3D-QSAR analysis, Hansch analysis, and Fujita-Ban analysis on a series of 5-arylidene-2,4-thiazolidinediones as aldose reductase inhibitors. The 2D & 3D-QSAR models were generated using 18 compounds and Fujita-Ban analysis models were obtained using 23 compounds. The predictive ability of the resulting 2D and 3D models was evaluated against a test set of 5 compounds. Analyses of results from the present QSAR study inferred that 3rd position of the phenyl ring and acetic acid substitution at N-position of thiazolidinediones play a key role in the aldose reductase inhibitory activity.
authors.affiliation: Molecular Modelling Study Group, CADD Laboratory, Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23 Park Road, Indore-452003, M.P., India.
authors.forename: S V
authors.initials: SV
authors.lastname: Sambasivarao
authors.forename: Love K
authors.initials: LK
authors.lastname: Soni
authors.forename: Arun K
authors.initials: AK
authors.lastname: Gupta
authors.forename: P
authors.initials: P
authors.lastname: Hanumantharao
authors.forename: S G
authors.initials: SG
authors.lastname: Kaskhedikar
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007908:Lens, Crystalline / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D000449:Aldehyde Reductase