Multivariate SAR/QSAR of 3-aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase (FAS) inhibitors.
Two multivariate studies, a PCA-SAR and a PLS-QSAR, of 3-aryl-4-hydroxyquinolin-2(1H)-one derivatives described as type I fatty acid synthase (FAS) inhibitors, are presented in this work. The variable selection was performed with the Fisher's weight and Ordered Predictors Selection (OPS) algorithm, respectively. In the PCA, a separation between active and inactive compounds was obtained by six descriptors (topological and geometrical). The PLS model presented five descriptors and two Latent Variables. Leave-N-out cross validation and y-randomization test showed that the model presented robustness and no chance correlation, respectively, and the descriptors indicated that the FAS inhibition depends on electronic distribution of the investigated compounds. The model obtained in this study may provide a guidance for proposition of new FAS inhibitors.
de Melo
Eduardo Borges
EB
LQMAT--Theoretical Medicinal and Environmental Chemistry Laboratory, Department of Pharmacy, Western Paraná State University, Unioeste, Cascavel, PR, 8519110, Brazil. ebmelo@unioeste.br
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors*; D006801:Humans; D006912:Hydroxyquinolines / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006912:Hydroxyquinolines; D054890:Fatty Acid Synthase, Type I; C034010:4-hydroxyquinoline