Drug Design, Development and Therapy (May 2016)
Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ
Abstract
Liang Ma,1,* Taijin Wang,2,* Min Shi,1 Haoyu Ye2 1Department of Nephrology, Kidney Research Institute, 2State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work 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
