title: Quantitative structure-activity relationship analysis of human neutrophil elastase inhibitors using shuffling classification and regression trees and adaptive neuro-fuzzy inference systems.
abstract: The purpose of this study was to develop quantitative structure-activity relationship models for N-benzoylindazole derivatives as inhibitors of human neutrophil elastase. These models were developed with the aid of classification and regression trees (CART) and an adaptive neuro-fuzzy inference system (ANFIS) combined with a shuffling cross-validation technique using interpretable descriptors. More than one hundred meaningful descriptors, representing various structural characteristics for all 51 N-benzoylindazole derivatives in the data set, were calculated and used as the original variables for shuffling CART modelling. Five descriptors of average Wiener index, Kier benzene-likeliness index, subpolarity parameter, average shape profile index of order 2 and folding degree index selected by the shuffling CART technique have been used as inputs of the ANFIS for prediction of inhibition behaviour of N-benzoylindazole derivatives. The results of the developed shuffling CART-ANFIS model compared to other techniques, such as genetic algorithm (GA)-partial least square (PLS)-ANFIS and stepwise multiple linear regression (MLR)-ANFIS, are promising and descriptive. The satisfactory results r2p = 0.845, Q2(LOO) = 0.861, r2(L25%O) = 0.829, RMSE(LOO)  = 0.305 and RMSE(L25%O)  = 0.336) demonstrate that shuffling CART-ANFIS models present the relationship between human neutrophil elastase inhibitor activity and molecular descriptors, and they yield predictions in excellent agreement with the experimental values.
authors.affiliation: Department of Science, Babol University of Technology, Babol, Iran. asadollahi@nit.ac.ir
authors.forename: M
authors.initials: M
authors.lastname: Asadollahi-Baboli
mesh_terms: D015195:Drug Design; D006801:Humans; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007191:Indazoles; D053491:Proteinase Inhibitory Proteins, Secretory; D019272:Leukocyte Elastase