Alpha-Substituted Derivatives of Cinnamaldehyde as Tyrosinase Inhibitors: Inhibitory Mechanism and Molecular Analysis

• Published in: Journal of agricultural and food chemistry Vol. 63; no. 2; pp. 716 - 722
• Main Authors: Cui, Yi, Liang, Ge, Hu, Yong-Hua, Shi, Yan, Cai, Yi-Xiang, Gao, Huan-Juan, Chen, Qing-Xi, Wang, Qin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.01.2015; American Chemical Society, Books and Journals Division
• Subjects: Acrolein - analogs & derivatives; Acrolein - chemistry; active sites; Agaricales - enzymology; amino acids; catechol oxidase; copper; Enzyme Inhibitors - chemistry; fluorescence; Fungal Proteins - antagonists & inhibitors; Fungal Proteins - chemistry; inhibitory concentration 50; Kinetics; Molecular Docking Simulation; molecular models; Molecular Structure; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - chemistry; mushrooms; derivatives of cinnamaldehyde; molecular docking; tyrosinase; fluorescence quenching
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf505469k

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 IC 50 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.