Novel Dihydrocoumarins Induced by Radiolysis as Potent Tyrosinase Inhibitors.

A representative naturally occurring coumarin, 4-methylumbelliferone ( 5 ), was exposed to 50 kGy of gamma ray, resulting in four newly generated dihydrocoumarin products 1 - 4 induced by the gamma irradiation. The structures of these new products were elucidated by interpretation of spectroscopic data (NMR, MS, [α] D , and UV). The unusual bisdihydrocoumarin 4 exhibited improved tyrosinase inhibitory capacity toward mushroom tyrosinase with IC 50 values of 19.8 ± 0.5 μM as compared to the original 4-methylumbelliferone ( 5 ). A kinetic analysis also exhibited that the potent metabolite 4 had non-competitive modes of action. Linkage of the hydroxymethyl group in the C-3 and C-4 positions on the lactone ring probably enhances the tyrosinase inhibitory effect of 4-methylumbelliferone ( 5 ). Thus, the novel coumarin analog 4 is an interesting new class of tyrosinase inhibitory candidates that requires further examination.