Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC₅₀) 0.75±0.20 μM, exhibited in vitro potency comparable with a 0.83±0.14 μM of the positive control rosiglitazone. Molecular docking and molecular dynamics simulations indicated that phenylthiazole acid 4t interacted with the amino acid residues of the active site of the PPARγ complex in a stable manner, consistent with the result of the in vitro ligand assay.

Keywords:

• PPARγ
• phenylthiazole acids
• ligand screening assay
• docking study

Acknowledgments

This research was supported by the Natural Science Foundation of China (no 81402782) and the China Postdoctoral Science Foundation (no 2015T80985).

Disclosure

The authors report no conflicts of interest in this work.