A New Tyrosinase Inhibitor from the Red Alga Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae)

A marine red alga, Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae), is a rich source of bromophenols with a wide array of biological activities. This study investigates the anti-tyrosinase activity of the alga. Moderate activity was demonstrated by the methanol extract of S. latiuscula, and subsequent column chromatography identified three bromophenols: 2,3,6-tribromo-4,5-dihydroxybenzyl methyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). Bromophenols 1 and 3 exhibited potent competitive tyrosinase inhibitory activity against l-tyrosine substrates, with IC(50) values of 10.78 ± 0.19 and 2.92 ± 0.04 μM, respectively. Against substrate l-3,4-dihydroxyphenylalanine (l-DOPA), compounds 1 and 3 demonstrated moderate activity, while 2 showed no observable effect. The experimental data were verified by a molecular docking study that found catalytic hydrogen and halogen interactions were responsible for the activity. In addition, compounds 1 and 3 exhibited dose-dependent inhibitory effects in melanin and intracellular tyrosinase levels in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Compounds 3 and 1 were the most effective tyrosinase inhibitors. In addition, increasing the bromine group number increased the mushroom tyrosinase inhibitory activity.