Molecular features related to the binding mode of PPARδ agonists from QSAR and docking analyses

Abstract

Diabetes affects approximately 4% of world’s population and metabolic syndrome has been directly related to obesity. There is a class of nuclear receptors, peroxisome proliferator-activated receptors (PPARs), which controls the metabolism of carbohydrates and lipids. It has been considered an attractive target to treat diabetes and metabolic syndrome. Accordingly, the primary objective of this study was to employ molecular modelling techniques to understand the factors involved in PPARδ activation. The QSAR models obtained showed good internal and external consistency and presented good validation coefficients (QSAR: q² = 0.83, r² = 0.87; HQSAR: q² = 0.73, r² = 0.90; CoMFA: q² = 0.88, r² = 0.94). The selected properties and the contour maps described the possible interactions between the PPARδ receptor and its agonists. From these findings, it is possible to propose molecular modifications to design new compounds with improved biological properties.

Keywords:

• PPARδ
• diabetes mellitus
• metabolic syndrome
• drug design
• molecular modelling

Acknowledgements

We would like to thank FAPESP (São Paulo Research Funding Body), CNPq (The National Council for Scientific and Technological Development) and CAPES (Coordination for the Improvement of High Education Personnel), Brazil, for providing the financial support needed in this research project.