Inhibitory effects of esculetin on melanin biosynthesis.
To investigate the structure-activity relationship of coumarins for the inhibitory activity on mushroom tyrosinase, the 50% inhibitory concentration (IC50 values) of 18 coumarins and four cinnamic acid derivatives were measured. Among these compounds, esculetin had the strongest inhibitory activity (IC50=43 microM) on mushroom tyrosinase. Introduction of a hydroxy group to the C6 and C7 positions of the coumarin ring and no substitution on the lactone ring played an important role in the expression of the strong inhibitory activity of esculetin. We performed further studies to estimate the in vitro inhibitory effects of esculetin on melanogenesis. Esculetin 5 microM significantly suppressed melanin production in murine B16 melanoma cells without affecting cell growth. Furthermore, the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes in the split-epidermal sheets treated with 0.05% or 0.1% esculetin was significantly lower than that in the control. From these results, it is suggested that esculetin has inhibitory effects on tyrosinase activity in vitro. However, further detailed studies are necessary to understand the inhibitory mechanism of esculetin.
Masamoto
Yukimitsu
Y
Graduate School of Natural Science and Technology, Okayama University, Tsushima-Naka, Okayama, Japan.
Murata
Yoshiyuki
Y
Baba
Kimiye
K
Shimoishi
Yasuaki
Y
Tada
Mikiro
M
Takahata
Kyoya
K
D000363:Agaricales / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D000078404:Epidermal Cells; D006168:Guinea Pigs; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D008546:Melanoma, Experimental; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D012878:Skin Neoplasms; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000737:chemistry / Q000494:pharmacology*
D008543:Melanins; D014468:Umbelliferones; D004295:Dihydroxyphenylalanine; D014442:Monophenol Monooxygenase; C007628:esculetin