Melanin Biosynthesis Inhibitors from Wood of Artocarpus heterophyllus: The Effect of Isoprenoid Substituent of Flavone with 4-Substituted Resorcinol Moiety at B Ring

In our efforts to find new whitening agent from natural resources, we focused on wood of Artocarpus heterophyllus which shows anti- melanogenesis activity. By activity- guided fractionation of A. heterophyllus wood extract, norartocarpetin (1) and artocarpesin (2) were isolated. These compounds have 4- substituted resorcinol moiety in B ring, which is an important substructure for revealing the tyrosinase inhibitory activity. Also, the effect of albanin A (3) which has 4- substituted resorcinol moiety at B ring with prenyl substituent at C-3 position, was examined for comparison. The IC50 values of mushroom tyrosinase inhibitory activity of norartocarpetin (1), artocarpesin (2) and albanin A (3) were 1.7, 8.5 and 463 mu M, respectively. In melanin formation inhibition on B16 melanoma cells, the IC50 of these compounds (1- 3) were 209.1, 45.1 and 40.1 mu M, respectively. The roles of each substructure of flavones having 4-substituted resorcinol moiety with or without prenyl substituent on tyrosinase and melanin biosynthesis in B16 melanoma cells were discussed.