Tyrosinase inhibitory effects of 1,3-diphenylpropanes from Broussonetia kazinoki

Abstract

Six 1,3-diphenylpropanes exhibiting inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase were isolated from the methanol (95%) extract of Broussonetia kazinoki. These compounds, 1-6, were identified as kazinol C (1), D (2), F (3), broussonin C (4), kazinol S (5) and kazinol T (6). The latter two species (5 and 6) emerged to be new 1,3-diphenylpropanes which we fully spectroscopically characterized. The IC50 values of compounds (1, 3-5) for monophenolase inhibition were determined to range between 0.43 and 17.9 mu M. Compounds 1 and 3-5 also inhibited diphenolase significantly with IC50 values of 22.8, 1.7, 0.57, and 26.9 mu M, respectively. All four active tyrosinase inhibitors (1, 3-5) were competitive inhibitors. Interestigly they all mainfested simple reversible slow-binding inhibition against diphenolase. The most potent inhibitor, compound 4 diplayed the following kinetic parameters k(3) = 0.0993 mu M (1) min (1), k(4) = 0.0048 min(-1), and K-i(app) = 0.0485 mu M.