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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 10, n. 3 MAR 13 2015.
• Web of Science Citations: 14

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 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)

• FAPESP's process: 11/18981-2 - Molecular modeling study employing 2D and 3D QSAR and molecular docking for PPARd agonists
• Grantee: Vinicius Gonçalves Maltarollo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/06565-2 - Extending the frontiers in biomolecular interactions: docking and free energy assessment
• Grantee: Alessandro Silva Nascimento
• Support Opportunities: Regular Research Grants