Synthesis and evaluation of 2′,4′,6′-trihydroxychalcones as a new class of tyrosinase inhibitors

In this study, we synthesized a series of hydroxychalcones and examined their tyrosinase inhibitory activity. The results showed that 2′,4′,6′-trihydroxychalcone (1), 2,2′,3,4′,6′-pentahydroxychalcone (4), 2′,3,4,4′,5,6′-hexahydroxychalcone (5), 2′,4′,6′-trihydroxy- 3,4-dimethoxychalcone (9) and 2,2′,4,4′,6′-pentahydroxychalcone (15) exhibited high inhibitory effects on tyrosinase with respect to l-tyrosine as a substrate. By the structure–activity relationship study, it was suggested that the 2′,4′,6′-trihydroxyl substructure in the chalcone skeleton were efficacious for the inhibition of tyrosinase activity. And also, the catechol structure on B-ring of chalcones was not advantageous for the inhibitory potency. Furthermore, 15 (IC50 = 1 μM) was found to show the highest activity out of a set of 15 hydroxychalcones, even better than both 2,2′,4,4′-tetrahydroxychalcone (13, IC50 = 5 μM) and kojic acid (16, IC50 = 12 μM), which were known as potent tyrosinase inhibitors. Kinetic study revealed that 15 acts as a competitive inhibitor of tyrosinase with Ki value of 3.1 μM.

A series of 2′,4′,6′-trihydroxychalcones were synthesized and their tyrosinase. Inhibitory effects were examined.Figure optionsDownload as PowerPoint slide