Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens.
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.
Ryu
Y B
YB
Department of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Westwood
I M
IM
Kang
N S
NS
Kim
H Y
HY
Kim
J H
JH
Moon
Y H
YH
Park
K H
KH
D001665:Binding Sites; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D029909:Sophora / Q000737:chemistry*; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism
D005419:Flavonoids; D008543:Melanins; D010455:Peptides; C526229:kurarinol