苯二醛缩氨基硫脲的合成及其酪氨酸酶抑制活性研究

目的 合成苯二醛单缩和二缩氨基硫脲类化合物，并初步研究其抑制酪氨酸酶的活性和作用机制。方法 以5种苯二醛和氨基硫脲为原料，通过缩合反应合成9个目标化合物；采用蘑菇酪氨酸酶多巴速率氧化法和酶抑制动力学实验，测定目标化合物对酪氨酸酶的抑制活性和作用机制；选择化合物3a和4a进行抑制机制和抑制动力学研究。结果 目标化合物的结构经¹H-NMR、¹³C-NMR及MS确证；所有化合物抑制酪氨酸酶的活性均优于对照药物曲酸；苯二醛二缩氨基硫脲3a~3d的活性明显强于相应的单缩氨基硫脲4a~4d；化合物3a和4a对酪氨酸酶的抑制作用均表现为混合型可逆抑制作用。结论 苯二醛二缩氨基硫脲类化合物具有优异的抑制酪氨酸酶的活性，值得进一步深入研究。

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.