New Class of Tyrosinase Inhibitors, Rotenoids, from Amorpha fruticosa .

A series of rotenoids including a new one from the seeds of Amorpha fruticosa were found to have significant potential as tyrosinase inhibitors. All of the isolated rotenoids ( 1-6 ) 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 ( 1 , 5 , and 6 ) showed significant monophenolase inhibition with IC 50 values of 2.1, 1.7, and 1.2 μM, respectively. They also inhibited diphenolase function with IC 50 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 E met ·I complex effectively around their IC 50 values with long lag times. Tyrosinase inhibition of the new rotenoid 6 was additionally demonstrated using high-performance liquid chromatography (HPLC) analysis with N -acetyl-l-tyrosine. Molecular docking disclosed that the sugar moiety of 5 interacted with the bottom of the catalytic gorge.