title: Quantitative structure-activity relationship study of aromatic inhibitors against rat lens aldose reductase activity using variable selections.
abstract: A quantitative structure-activity relationship (QSAR) study of aromatic inhibitors against aldose reductase (AR) activity was performed using variable selection from stepwise multiple linear regression (MLR) and genetic algorithm (GA)-MLR. As a result of variable selection, stepwise MLR and GA-MLR gave the same results with one, two, three and five descriptors and different results with four and six descriptors. GA-MLR produced higher values and was better in explanatory and predictive power than stepwise MLR in four variables. AR activity (pIC50) of aromatic derivatives was expressed with acceptable explanatory (74.6-81.2%) and predictive power (68.8-74.4%) in models 3 and 4. The resulting models with the given descriptors illustrate that hydrophobic and electrostatic interactions play a significant role in inhibition of AR activity. This study suggests that the QSAR models can be used as guidelines to predict improved aldose reductase inhibitory activity and to obtain reliable predictions in structurally diverse compounds.
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea. mjung@yonsei.ac.kr
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
authors.forename: Yongnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Minjoo
authors.initials: M
authors.lastname: Shim
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lim
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007908:Lens, Crystalline / Q000201:enzymology*; D008954:Models, Biological; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase