title: Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase.
abstract: 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 IC50values 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.
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Hu
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China.
authors.forename: Lin-Shan
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China; Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005, China.
authors.forename: Qing-Xi
authors.initials: QX
authors.lastname: Chen
authors.affiliation: Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, School of Life Sciences, Xiamen 361005, China. Electronic address: qwang@xmu.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000363:Agaricales / Q000737:chemistry / Q000201:enzymology; D020134:Catalytic Domain; D002413:Cations, Divalent; D002934:Cinnamates / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000737:chemistry
chemical_list: D002413:Cations, Divalent; D002934:Cinnamates; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C029010:cinnamic acid; D014443:Tyrosine; D007980:Levodopa; D003300:Copper; D014442:Monophenol Monooxygenase
keywords: Derivatives of cinnamic acid; Fluorescence spectra; Molecular simulation