title: Structure-based virtual screening and discovery of New PPARδ/γ dual agonist and PPARδ and γ agonists.
abstract: Peroxisome proliferator-activated receptors (PPARs) are involved in the control of carbohydrate and lipid metabolism and are considered important targets to treat diabetes mellitus and metabolic syndrome. The available PPAR ligands have several side effects leading to health risks justifying the search for new bioactive ligands to activate the PPAR subtypes, in special PPARδ, the less studied PPAR isoform. Here, we used a structure-based virtual screening protocol in order to find out new PPAR ligands. From a lead-like subset of purchasable compounds, we identified 5 compounds with potential PPAR affinity and, from preliminary in vitro assays, 4 of them showed promising biological activity. Therefore, from our in silico and in vitro protocols, new PPAR ligands are potential candidates to treat metabolic diseases.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brasil; Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, São Paulo, Brasil.
authors.forename: Vinicius G
authors.initials: VG
authors.lastname: Maltarollo
authors.affiliation: Faculdade de Ciências da Saúde, Universidade de Brasília, Brasília, Distrito Federal, Brasil.
authors.forename: Marie
authors.initials: M
authors.lastname: Togashi
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, São Paulo, Brasil.
authors.forename: Alessandro S
authors.initials: AS
authors.lastname: Nascimento
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brasil; Escola de Artes Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brasil.
authors.forename: Kathia M
authors.initials: KM
authors.lastname: Honorio
mesh_terms: D018360:Crystallography, X-Ray; D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D054333:Drug Partial Agonism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D047494:PPAR delta; D047495:PPAR gamma