Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase

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• 作者：Yi Cui^a ; Yong-Hua Hu^a ; Feng Yu^a ; Jing Zheng^a ; Lin-Shan Chen^a ; Qing-Xi Chen^a ; ^b ; Qin Wang^a ; ^{qwang@xmu.edu.cn}
• 关键词：4-CCA ; 4-chlorocinnamic acid ; 4-ECA ; 4-ethoxycinnamic acid ; 4-NCA ; 4-nitrocinnamic acid ; DMSO ; dimethyl-sulfoxide ; L-Tyr ; L-tyrosine ; L-DOPA ; L-3 ; 4-Dihydroxyphenylalanine ; Km ; Michaelis-Menten constant ; KI ; equilibrium constant of the inhibitor combining with the free enzyme ; IC50 ; inhibitor concentration leading to a 50% loss of activity
• 刊名：International Journal of Biological Macromolecules
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：95
• 期：Complete
• 页码：1289-1297
• 全文大小：1446 K
• 卷排序：95

文摘

This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV–vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors.