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 I competed with L-tyrosine for tyrosinase. Compound I also suppressed melanogenesis in a human skin model (up to 49% at 2.8 mu mol/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.