Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ.
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.
Department of Nephrology, Kidney Research Institute, West China Medical School of Sichuan University, Chengdu, People's Republic of China.
Liang
L
Ma
State 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.
Taijin
T
Wang
Department of Nephrology, Kidney Research Institute, West China Medical School of Sichuan University, Chengdu, People's Republic of China.
Min
M
Shi
State 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.
Haoyu
H
Ye
D000818:Animals; D008024:Ligands; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D008024:Ligands; D047495:PPAR gamma; D013844:Thiazoles
PPARγ; docking study; ligand screening assay; phenylthiazole acids