Structure-Based Virtual Screening and Discovery of New PPAR delta/gamma Dual Agonist and PPAR delta and gamma Agonists

Autor(es)

Maltarollo, Vinicius G. ^{[1, 2]} ; Togashi, Marie ^[3] ; Nascimento, Alessandro S. ^[4] ; Honorio, Kathia M. ^{[5, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo - Brazil

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Sao Paulo - Brazil

^[3] Univ Brasilia, Fac Ciencias Saude, Brasilia, DF - Brazil

^[4] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 3 MAR 13 2015.
• Citações Web of Science: 14

Resumo

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 PPAR delta, 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. (AU)

• Processo FAPESP: 11/18981-2 - Estudos de modelagem molecular empregando métodos de QSAR 2D, 3D e docagem molecular para compostos com afinidade pelo receptor PPARd
• Beneficiário: Vinicius Gonçalves Maltarollo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/06565-2 - Estendendo as fronteiras em interações biomoleculares: docking e avaliação da energia livre
• Beneficiário: Alessandro Silva Nascimento
• Modalidade de apoio: Auxílio à Pesquisa - Regular