Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens

Phytomedicine. 2008 Aug;15(8):612-8. doi: 10.1016/j.phymed.2007.09.022. Epub 2007 Oct 24.

Abstract

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 microg/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 microM) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Melanins / biosynthesis
  • Models, Molecular
  • Molecular Structure
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Plant Roots / chemistry*
  • Sophora / chemistry*
  • Streptomyces / drug effects
  • Streptomyces / metabolism

Substances

  • Flavonoids
  • Melanins
  • Peptides
  • kurarinol