Novel inhibitors of tyrosinase produced by the 4-substitution of TCT.

We synthesized a series of 4- or 5-functionalized TCT derivatives (1-12) and investigated their inhibitory activities and mechanisms on tyrosinase by using Spectrofluorimetry, 1H and 13C NMR titration and IR spectra. The results of the fluorescence spectra and NMR titrations showed that the thiosemicarbazone moiety formed complexes with copper ions in the active center of the enzyme and played an important role in inhibiting the activities of the target compounds. The 5-functionalization decreased the inhibitory activity, but the 4-functionalization with a methoxyacetyl group enhanced the inhibitory activity, in which a strong auxiliary vicinity synergistic effect from the methoxyacetyl group strengthens and promotes the formation of complexes between the sulfur atoms of the inhibitor and the dicopper nucleus of tyrosinase. We concluded that the appropriate 4-functionalization improved the inhibitory activity of the modifier, and that 4-methoxyacetyl -TCT is promising for the inhibition of tyrosinase.