Synthesis and Tyrosinase Inhibitory Activities of Phthalaldehyde Thiosemicarbazones

OBJECTIVE To synthesize phthalaldehyde mono-and dithiosemicarbazones and evaluate their tyrosinase inhibitory activities and inhibition mechanisms. METHODS Nine target compounds were synthesized through condensation reaction between thiosemicarbazide and 5 phthalaldehydes. The tyrosinase inhibitory activities and mechanisms of the target compounds were determined by measuring the rate of oxidation of L-3-hydroxytyrosine(L-DOPA) and enzyme inhibition kinetics experiment, respectively. The inhibition mechanisms and kinetics of selected compounds 3a and 4a were investigated. RESULTS The structures of the target compounds were confirmed by ¹H-NMR, ¹³C-NMR and MS. The activity test showed that all the obtained compounds displayed potent tyrosinase inhibitory activity more than kojic acid, and the phthalaldehyde dithiosemicarbazones 3a-3d showed significantly stronger activity than the corresponding monothiosemicarbazones 4a-4d. Compounds 3a and 4a were belonged to the reversible and mixed type tyrosinase inhibitors. CONCLUSION The phthalaldehyde dithiosemicarbazones have excellent tyrosinase inhibitory activity, which deserve further study.