Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens

• Published in: Phytomedicine (Stuttgart) Vol. 15; no. 8; pp. 612 - 618
• Main Authors: Ryu, Y.B., Westwood, I.M., Kang, N.S., Kim, H.Y., Kim, J.H., Moon, Y.H., Park, K.H.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.08.2008; Urban & Fischer Verlag
• Subjects: Binding Sites; Bioflavonoids; Chemical properties; Control; Flavones; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Health aspects; Identification and classification; Kurarinol; Lavandulylated flavanone; Melanins - biosynthesis; Models, Molecular; Molecular modeling; Molecular Structure; Mushroom tyrosinase; Peptides - chemistry; Peptides - pharmacology; Physiological aspects; Plant Roots - chemistry; Protein tyrosine kinase; Root of Sophora flavescens; Sophora - chemistry; Streptomyces - drug effects; Streptomyces - metabolism; South Korea; Kurarinol; Mushroom tyrosinase; Lavandulylated flavanone; Molecular modeling; Root of Sophora flavescens
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2007.09.022

It is well known that flavanones, sophoraflavanone G 1, kurarinone 2, and kurarinol 3, from the root of Sophora flavescens, have extremely strong tyrosinase inhibitory activity. This study delineates the principal pharmacological features of kurarinol 3 that lead to inhibition of the oxidation of l-tyrosine to melanin by mushroom tyrosinase (IC 50 of 100 nM). The inhibition kinetics analyses unveil that compounds 1 and 2 are noncompetitive inhibitors. However similar analysis shows kurarinol 3 to be a competitive inhibitor. Compounds 1 and 2 exhibited potent antibacterial activity with 10 μg/disk against Gram-positive bacteria, whereas kurarinol 3 did not ostend any antibacterial activity. Interestingly, kurarinol 3 inhibits production of melanin in S. bikiniensis without affecting the growth of microorganism. It is thus distinctly different from the other tyrosinase inhibitors 1 and 2. In addition, kurarinol 3 manifests relatively low cytotoxic activity (EC 50>30 μM) compared to 1 and 2. To account for these observations, we conducted molecular modeling studies. These suggested that the lavandulyl group within 3 is instrumental in the interaction with the enzyme. More specifically, the terminal hydroxy function within the lavandulyl group is most important for optimal binding.