Effects of hydroxystilbene derivatives on tyrosinase activity.
Synthesis of melanin starts from the conversion of L-tyrosine to 3,4-dihydroxyphenylalanine (L-dopa) and then the oxidation of L-dopa yields dopaquinone by tyrosinase. Therefore, tyrosinase inhibitors have been established as important constituents of depigmentation agents. Recently, polyhydroxystilbene compounds, which are trans-resveratrol (3,4('),5-trihydroxy-trans-stilbene) analogs, have been demonstrated as potent tyrosinase inhibitors. However, their detailed inhibitory mechanisms are not clearly understood. In the present study, a variety of synthesized hydroxystilbene compounds were tested for their inhibitory effects against murine tyrosinase activity. The inhibitory potencies of the hydroxy-trans-stilbene compounds were remarkably elevated by increasing number of phenolic hydroxy substituents. Methylated hydroxy-trans-stilbene lost the inhibitory activity. Furthermore, hydrogenated hydroxystilbene or hydroxy-cis-stilbene exerted little or no inhibitory effect compared with hydroxy-trans-stilbene on tyrosinase activity. The structure-activity relationships demonstrated in the present study suggest that the phenolic hydroxy groups and trans-olefin structure of the parent stilbene skeleton contribute to the inhibitory potency of hydroxystilbene for tyrosinase activity.
Ohguchi
Kenji
K
Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. kohguchi@giib.or.jp
Tanaka
Toshiyuki
T
Kido
Tadashi
T
Baba
Kimiye
K
Iinuma
Munekazu
M
Matsumoto
Kenji
K
Akao
Yukihiro
Y
Nozawa
Yoshinori
Y
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D013267:Stilbenes; D014442:Monophenol Monooxygenase