A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.

Abstract

During the search for naturally occurring cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) inhibitors, it was found that the extracts from Sophora flavescens exhibit potent inhibitory activity against cGMP PDE5 prepared from rat diaphragm. Therefore, the inhibitory activities of five flavonoids, kushenol H (1), kushenol K (2), kurarinol (3), sophoflavescenol (4) and kuraridine (5), isolated from S. flavescens were measured against cGMP PDE5 to identify potent cGMP PDE5 inhibitory constituents. Among tested compounds, sophoflavescenol (4), a C-8 prenylated flavonol, showed the most potent inhibitory activity (IC(50)=0.013 microM) against cGMP PDE5 with 31.5- and 196.2-fold selectivity over PDE3 and PDE4, respectively. Kinetic analysis revealed that sophoflavescenol was a mixed inhibitor of PDE5 with a K(i) value of 0.005 microM.

Cite this paper

@article{Shin2002APF, title={A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.}, author={Hye Joo Shin and Hyoung Ja Kim and Jong Hwan Kwak and Hyung O K Chun and Je Hak Kim and Hokoon Park and Dong Hyun Kim and Yong Sup Lee}, journal={Bioorganic & medicinal chemistry letters}, year={2002}, volume={12 17}, pages={2313-6} }