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Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPAR?.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPAR? 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 PPAR? ligand screening assay. Compound 4t, as a potential PPAR? agonist with half maximal effective concentration (EC50) 0.75±0.20 ?M, exhibited in vitro potency comparable with a 0.83±0.14 ?M 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 PPAR? complex in a stable manner, consistent with the result of the in vitro ligand assay.

SUBMITTER: Ma L

PROVIDER: S-EPMC4892293 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Ma Liang L Wang Taijin T Shi Min M Ye Haoyu H

Drug design, development and therapy 20160530

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 ...[more]

PMID: 27313447

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