New Class of Tyrosinase Inhibitors, Rotenoids, from .

A series of rotenoids including a new one from the seeds of were found to have significant potential as tyrosinase inhibitors. All of the isolated rotenoids () displayed inhibitory activity against tyrosinase, both as a monophenolase for the oxidation of l-tyrosine and as a diphenolase for the oxidation of l-DOPA. The three most active compounds (, , and ) showed significant monophenolase inhibition with IC values of 2.1, 1.7, and 1.2 μM, respectively. They also inhibited diphenolase function with IC values in the range of 9.5-21.5 μM. The inhibition kinetics established all compounds to be competitive inhibitors of both oxidation processes. All rotenoids formed the ·I complex effectively around their IC values with long lag times. Tyrosinase inhibition of the new rotenoid was additionally demonstrated using high-performance liquid chromatography (HPLC) analysis with -acetyl-l-tyrosine. Molecular docking disclosed that the sugar moiety of interacted with the bottom of the catalytic gorge.