kurarinol and sophoflavescenol

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.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 3; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Enzyme Inhibitors; Flavonoids; Inhibitory Concentration 50; Kinetics; Rats; Sophora; Structure-Activity Relationship

A new prenylated flavonol, sophoflavescenol (1), together with five known flavonoids, kurarinol, kushenol K, kushenol H, trifolirhizin, and kuraidin, were isolated from the roots of Sophora flavescens. The structure of 1 was determined by spectroscopic analysis. Among the five known flavonoids, kurarinol, kushenol K, and kushenol H showed weak antiviral activity against Herpes simplex virus types I and II.

Topics: Antiviral Agents; China; Flavonoids; Herpesvirus 1, Human; Herpesvirus 2, Human; Magnetic Resonance Spectroscopy; Mass Spectrometry; Plant Roots; Plants, Medicinal; Spectrophotometry, Ultraviolet