Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.
Keywords: antimelanogenic; biocatalysis; molecular docking; tyrosinase inhibition.