title: Role of physicochemical properties in the activation of peroxisome proliferator-activated receptor δ.
abstract: Current researches on treatments for metabolic diseases involve a class of biological receptors called peroxisome proliferator-activated receptors (PPARs), which control the metabolism of carbohydrates and lipids. A subclass of these receptors, PPARδ, regulates several metabolic processes, and the substances that activate them are being studied as new drug candidates for the treatment of diabetes mellitus and metabolic syndrome. In this study, several PPARδ agonists with experimental biological activity were selected for a structural and chemical study. Electronic, stereochemical, lipophilic and topological descriptors were calculated for the selected compounds using various theoretical methods, such as density functional theory (DFT). Fisher's weight and principal components analysis (PCA) methods were employed to select the most relevant variables for this study. The partial least squares (PLS) method was used to construct the multivariate statistical model, and the best model obtained had 4 PCs, q                         (                            2                         ) = 0.80 and r                         (                            2                         ) = 0.90, indicating a good internal consistency. The prediction residues calculated for the compounds in the test set had low values, indicating the good predictive capability of our PLS model. The model obtained in this study is reliable and can be used to predict the biological activity of new untested compounds. Docking studies have also confirmed the importance of the molecular descriptors selected for this system.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil.
authors.forename: Vinícius G
authors.initials: VG
authors.lastname: Maltarollo
authors.forename: Paula
authors.initials: P
authors.lastname: Homem-de-Mello
authors.forename: Káthia M
authors.initials: KM
authors.lastname: Honorio
mesh_terms: D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008024:Ligands; D047494:PPAR delta