Development of 6-arylcoumarins as nonsteroidal progesterone antagonists. Structure-activity relationships and fluorescence properties.
Basic Information
ID: ALA3861998
Journal: Bioorg Med Chem
Title: Development of 6-arylcoumarins as nonsteroidal progesterone antagonists. Structure-activity relationships and fluorescence properties.
Authors: Kinoshita M, Negishi M, Sakai H, Hirano T, Mori S, Fujii S, Kagechika H, Tanatani A.
Abstract: 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: 34nM) and 10b (IC50: 24nM) showed more potent PR-antagonistic activity than lead compounds 5 (IC50: 500nM) and 6 (IC50: 65nM) 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. These results indicate that 6-arylcoumarin will be a useful scaffold for PR antagonists and fluorescent probes targeting PR.
CiteXplore: 27665178
DOI: 10.1016/j.bmc.2016.09.020
Patent ID: ┄