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

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 μM. Compounds 1 and 3–5 also inhibited diphenolase significantly with IC₅₀ values of 22.8, 1.7, 0.57, and 26.9 μM, 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 k₃ = 0.0993 μM^?1 min^?1, k₄ = 0.0048 min^-1, and K_i^app = 0.0485 μM.