State Key Laboratory of Cellular Stress Biology and Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University , Xiamen 361102, China.
J Agric Food Chem. 2015 Jan 21;63(2):716-22. doi: 10.1021/jf505469k. Epub 2015 Jan 7.
Alpha-substituted derivatives of cinnamaldehyde (alpha-bromocinnamaldehyde, alpha-chlorocinnamaldehyde, and alpha-methylcinnamaldehyde) were used as inhibitors on mushroom tyrosinase. The result showed that three compounds can reduce both monophenolase and diphenolase activity on tyrosinase, and the inhibition was reversible. The IC50 values of alpha-bromocinnamaldehyde, alpha-chlorocinnamaldehyde, and alpha-methylcinnamaldehyde were 0.075, 0.140, and 0.440 mM on monophenolase and 0.049, 0.110, and 0.450 mM on diphenolase, respectively. The inhibition types and constants on diphenolase for these inhibitors were further studied. The molecular inhibition mechanisms of tyrosinase by the derivatives were investigated by UV-scanning study, fluorescence quenching, and molecular docking. These assays demonstrated that the derivatives could decrease the formation of o-quinones, and all derivatives were static quenchers of mushroom tyrosinase. Docking results implied that they could not form metal interactions with the copper ions of the enzyme, whereas they could interact with the amino acid residues of active site center. This research on alpha-substituted derivatives of cinnamaldehyde as tyrosinase inhibitors would lead to advances in the field of antityrosinase.
肉桂醛的α-取代衍生物（α-溴代肉桂醛、α-氯代肉桂醛和α-甲基肉桂醛）被用作蘑菇酪氨酸酶的抑制剂。结果表明，这三种化合物都能降低酪氨酸酶的单酚酶和二酚酶活性，且抑制作用是可逆的。α-溴代肉桂醛、α-氯代肉桂醛和α-甲基肉桂醛对单酚酶的 IC50 值分别为 0.075、0.140 和 0.440mM，对二酚酶的 IC50 值分别为 0.049、0.110 和 0.450mM。进一步研究了这些抑制剂对二酚酶的抑制类型和常数。通过紫外扫描研究、荧光猝灭和分子对接研究了这些衍生物对酪氨酸酶的分子抑制机制。这些实验表明，这些衍生物可以减少邻醌的形成，并且都是蘑菇酪氨酸酶的静态猝灭剂。对接结果表明，它们不能与酶的铜离子形成金属相互作用，而可以与活性中心的氨基酸残基相互作用。这项关于肉桂醛α-取代衍生物作为酪氨酸酶抑制剂的研究将推动抗酪氨酸酶领域的发展。
