In this study, we designed and synthesized eight
thiophene chalcone derivatives (1a⁻h) as
tyrosinase inhibitors and evaluated their mushroom
tyrosinase inhibitory activities. Of these eight compounds, (E)-3-(2,4-dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one (1c) showed strong competitive inhibition activity against mushroom
tyrosinase with IC50 values of 0.013 μM for
tyrosine hydroxylase and 0.93 μM for
dopa oxidase. In addition, we used
enzyme kinetics study and docking program to further evaluate the inhibitory mechanism of 1c toward
tyrosinase. As an underlying mechanism of 1c mediated anti-melanogenic effect, we investigated the inhibitory activity against
melanin contents and cellular
tyrosinase in B16F10
melanoma cells. As the results, the
enzyme kinetics and docking results supports that 1c highly interacts with
tyrosinase residues in the
tyrosinase active site and it can directly inhibit
tyrosinase as competitive inhibitor. In addition, 1c exhibited dose-dependent inhibitory effects in
melanin contents and intracellular
tyrosinase on α-
MSH and
IBMX-induced B16F10 cells. Overall, our results suggested that 1c might be considered potent
tyrosinase inhibitor for use in the development of therapeutic agents for diseases associated with hyperpigment disorders.