title: Improving the inhibitory activity of arylidenaminoguanidine compounds at the N-methyl-D-aspartate receptor complex from a recursive computational-experimental structure-activity relationship study.
abstract: Using a combination of both the partial least squares (PLS) and back-propagation artificial neural network (ANN) pattern recognition methods, several models have been developed to predict the activity of a series of arylidenaminoguanidine analogs as inhibitory modulators of the N-methyl-D-aspartate receptor complex. This was done by correlating structural and physicochemical descriptors obtained from computation software with the experimentally observed [(3)H]MK-801 displacement ability of a small library of synthesized and in vitro screened arylidenaminoguanidines. Results for the generated PLS model were r(2)=0.814, rmsd=0.208, rCV(2)=0.714, loormsd=0.261. The ANN model was created utilizing the eleven descriptors from the PLS model for comparison. The quality of the ANN model (r(2)=0.828, rmsd=0.200, rCV(2)=0.721, loormsd=0.257) is similar to the PLS model, and indicates that the feature between the inputs and the output is majorly linear. These computational models were able to predict inhibition of the NMDA receptor complex by this series of compounds in silico, affording a predictive structure-based 'pre-screening' paradigm for the arylideneaminoguanidine analogs.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors: Joshua R
authors: JR
authors: Ring
authors: Fang
authors: F
authors: Zheng
authors: Aaron J
authors: AJ
authors: Haubner
authors: John M
authors: JM
authors: Littleton
authors: Peter A
authors: PA
authors: Crooks
mesh_terms: D003198:Computer Simulation; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D016018:Least-Squares Analysis; D008954:Models, Biological; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D006146:Guanidines; D016194:Receptors, N-Methyl-D-Aspartate; C004479:pimagedine