Slow-Binding Inhibition of Tyrosinase by Ecklonia cava Phlorotannins.

Tyrosinase inhibitors improve skin whitening by inhibiting the formation of melanin precursors in the skin. The inhibitory activity of seven phlorotannins (1-7), triphlorethol A (1), eckol (2), 2-phloroeckol (3), phlorofucofuroeckol A (4), 2-O-(2,4,6-trihydroxyphenyl)-6,6'-bieckol (5), 6,8'-bieckol (6), and 8,8'-bieckol (7), from Ecklonia cava was tested against tyrosinase, which converts tyrosine into dihydroxyphenylalanine. Compounds 3 and 5 had IC50 values of 7.0 ± 0.2 and 8.8 ± 0.1 µM, respectively, in competitive mode, with Ki values of 8.2 ± 1.1 and 5.8 ± 0.8 µM. Both compounds showed the characteristics of slow-binding inhibitors over the time course of the enzyme reaction. Compound 3 had a single-step binding mechanism and compound 5 a two-step-binding mechanism. With stable AutoDock scores of -6.59 and -6.68 kcal/mol, respectively, compounds 3 and 5 both interacted with His85 and Asn260 at the active site.