title: Development of docking-based 3D-QSAR models for PPARgamma full agonists.
abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) has become an attractive molecular target for drugs that aim to treat diabetes mellitus type II, and its therapeutic potency against skin cancer and other skin diseases is also currently being explored. To study the relationship between the structure of several PPARγ full agonists and the trans-activation activity of PPARγ, we have performed a three-dimensional quantitative structure-activity relationship (3D-QSAR) study of tyrosine-based derivatives, based on the 3D alignment of conformations obtained by docking. Highly predictive 3D-QSAR models, with Pearson-R values of 0.86 and 0.90, were obtained for the transactivation activity and binding affinity of PPARγ, respectively. These models are in good agreement with the structural characteristics of the binding pocket of PPARγ and provide some structural insights for the improvement of PPARγ full agonist bioactivities.
authors.affiliation: Grup de Recerca en Nutrigenòmica, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, C/ Marcel. lí Domingo s/n, 43007 Tarragona, Catalonia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Guasch
authors.forename: Esther
authors.initials: E
authors.lastname: Sala
authors.forename: Cristina
authors.initials: C
authors.lastname: Valls
authors.forename: Miquel
authors.initials: M
authors.lastname: Mulero
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
authors.forename: Santiago
authors.initials: S
authors.lastname: Garcia-Vallvé
mesh_terms: D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D047495:PPAR gamma / Q000819:agonists / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma