Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay.

Chisato Yoshikawa, Hiroaki Ishida, Nami Ohashi, Toshimasa Itoh

International journal of molecular sciences 2021 Apr 14

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Peroxisome proliferator-activated receptor γ (PPARγ) is a molecular target of metabolic syndrome and inflammatory disease. PPARγ is an important nuclear receptor and numerous PPARγ ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARγ agonist rosiglitazone and used the compound in a binding assay for PPARγ. PPARγ-ligand-incorporated 7-methoxycoumarin, 1, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, 2, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand 2 maintained the rosiglitazone activity. The obtained partial agonist 6 appeared to act through a novel mechanism. The fluorescence intensity of 2 and 6 increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.

Citation

Chisato Yoshikawa, Hiroaki Ishida, Nami Ohashi, Toshimasa Itoh. Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay. International journal of molecular sciences. 2021 Apr 14;22(8)