Daedalin A, a metabolite of Daedalea dickinsii, inhibits melanin synthesis in an in vitro human skin model.
The culture broth of Daedalea dickinsii was found to predominantly contain the tyrosinase inhibitor, (2R)-6-hydroxy-2-hydroxymethyl-2-methyl-2H-chromene, daedalin A (1). Ongoing research into bioactive metabolites resulted in the identification of two new 2H-chromenes, 6-hydroxy-5,7-dimethoxy-2,2-dimethyl-2H-chromene (3) and 6-hydroxy-2-hydroxymethyl-5-methoxy-2-methyl-2H-chromene (4), together with 6-hydroxy-2,2-dimethyl-2H-chromene (2). Comparative studies of isolated compounds 1-4 and related compounds (+/-)-1 and 1a-1c showed 1 to have the strongest tyrosinase inhibitory activity. These results suggest that the hydroxyl groups at positions 6 and 9 of 1 were important for the potent activity. A Lineweaver-Burk plot for a kinetic analysis indicates that 1 competed with L-tyrosine for tyrosinase. Compound 1 also suppressed melanogenesis in a human skin model (up to 49% at 2.8 micromol/tissue application) without affecting the cell viability. Compounds 1, 1b and 1c also showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity comparable to that of alpha-tocopherol.
Morimura
Keiji
K
Interdisciplinary Graduate School of Science and Technology, Shinshu University, Nagano, Japan.
Hiramatsu
Kenji
K
Yamazaki
Chihiro
C
Hattori
Yasunao
Y
Makabe
Hidefumi
H
Hirota
Mitsuru
M
D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D055453:Coriolaceae / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D010851:Picrates / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*
D001578:Benzopyrans; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D008543:Melanins; D010851:Picrates; C526356:daedalin A; C004931:1,1-diphenyl-2-picrylhydrazyl; D014442:Monophenol Monooxygenase