Silybin Derivatives Produced by γ-Irradiation and Their Tyrosinase Inhibitory Activities.

Silybin, which belongs to the flavonolignan group, is the major component of the fruit extract of Silybum marianum (common name: milk thistle). Silybin is a medicinal compound with hepatoprotective, antioxidant, and anticancer properties. In this study, silybin derivatives were produced through γ-radiolysis, and their tyrosinase inhibitory activities were evaluated to explore the enhanced activities of silybin derivatives compared to silybin (1). Isosilandrin (2) and 2,3-dehydrosilybin (3) were obtained from a silybin sample irradiated at 300 kGy. The optimal dose showed significant changes in radiolysis product content. Compounds 2 and 3 exhibited an IC(50) of 274.6 and 109.5 μM, respectively, which are more potent than that of 1 (IC(50) > 500 μM). In addition, a molecular docking simulation revealed the binding affinity of these compounds to tyrosinase and their mechanisms of inhibition. Thus, γ-irradiation is an effective method for structural modification of silybin. We also demonstrated that 2,3-dehydrosilybin is a potential tyrosinase inhibitor.