Development of 6-arylcoumarins as nonsteroidal progesterone antagonists. Structure-activity relationships and fluorescence properties

作者：Kinoshita Marie; Negishi Mai; Sakai Haruka; Hirano Tomoya; Mori Shuichi; Fujii Shinya; Kagechika Hiroyuki; Tanatani Aya^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(21): 5602-5610.

DOI：10.1016/j.bmc.2016.09.020

• Progesterone
• Antagonist
• Fluorescent ligand
• Coumarin

Progesterone is involved in multiple physiological processes, including female reproduction, via binding to the progesterone receptor (PR). We have developed 6-arylcoumarins such as 5 and 6 as non-steroidal PR antagonists with receptor-binding-dependent fluorescence. In this study, we investigated the structure activity relationships and fluorescence properties of coumarin derivatives bearing a heterocyclic aromatic moiety. Among these derivatives, 7c (IC50: 34 nM) and 10b (IC50: 24 nM) showed more potent PR-antagonistic activity than lead compounds 5 (IC50: 500 nM) and 6 (IC50: 65 nM) in alkaline phosphatase (AP) assay. Compound 9b showed solvent-dependent fluorescence intensity, exhibiting strong fluorescence in the presence of PR LBD only in buffer solution. On the other hand, 10b showed a solvent-dependent shift of the fluorescence maximum wavelength in the presence of PR LBD.

• 出版日期2016-11-1