Dawson结构的多金属氧酸盐对酪氨酸酶的抑制作用

doi:10.11944/j.issn.1000-0518.2017.01.160094

摘要/Abstract

摘要：

按文献方法合成了两种Dawson结构的多金属氧酸盐,并对其结构进行紫外光谱和红外光谱分析。以H₆[P₂Mo₁₈O₆₂]和H₈[P₂Mo₁₇Cr(OH₂)O₆₁](简写为P₂Mo₁₈和P₂Mo₁₇Cr)为效应物,采用紫外分光光度法和酶动力学方法研究两种Dawson结构的多金属氧酸盐效应物对蘑菇酪氨酸酶二酚酶活性的抑制作用。结果表明,P₂Mo₁₈和P₂Mo₁₇Cr对酪氨酸酶二酚酶均具有显著的抑制效果,测定抑制酪氨酸酶活力下降50%的抑制浓度(IC₅₀)分别为(0.482±0.009) mmol/L和(0.503±0.011) mmol/L。动力学分析表明,P₂Mo₁₈和P₂Mo₁₇Cr对酪氨酸酶的抑制作用均表现为可逆的竞争型,抑制常数K_I分别为0.212和0.249 mmol/L。其中,综合考虑IC₅₀值和抑制常数,P₂Mo₁₈对酪氨酸酶二酚酶活性的抑制效果略优于P₂Mo₁₇Cr。

关键词: 酪氨酸酶, 抑制剂, 多金属氧酸盐, 二酚酶活性

Abstract:

Tyrosinase is a complicated copper containing oxidoreductase that is common in microorganism, plants, animals and human body, which plays a crucial role in melanin biosynthesis. Currently researches about tyrosinase inhibitors are mostly focused on natural extracts and organism. However, inorganic Dawson type polyoxometalates as tyrosinase inhibitors have been less reported. Two kinds of Dawson type polyoxometalates were synthesized and characterized by ultraviolet spectroscopy and infrared spectral analysis. The inhibitory effects of H₆[P₂Mo₁₈O₆₂] and H₈[P₂Mo₁₇Cr(OH₂)O₆₁](abbreviated to P₂Mo₁₈ and P₂Mo₁₇Cr, respectively) on mushroom tyrosinase were investigated by ultraviolet spectrophotometry and enzymatic kinetics methods. P₂Mo₁₈ and P₂Mo₁₇Cr have significant inhibitory effects on tyrosinase, and the IC₅₀ values of P₂Mo₁₈ and P₂Mo₁₇Cr are (0.482±0.009) mmol/L and (0.503±0.011) mmol/L for diphenolase, respectively. Enzymatic kinetics analysis indicates that P₂Mo₁₈ and P₂Mo₁₇Cr are reversible and competitive inhibitor, and the inhibition constant of P₂Mo₁₈ and P₂Mo₁₇Cr are 0.212 mmol/L and 0.249 mmol/L, respectively. Considering of IC₅₀ values and inhibition constants, the inhibitory effect of P₂Mo₁₈ is slightly better than that of P₂Mo₁₇Cr. In conclusion, P₂Mo₁₈ and P₂Mo₁₇Cr show effective antityrosinase activities. Compared with arbutin, P₂Mo₁₈ and P₂Mo₁₇Cr have much more inhibitory effects on the diphenolase activity of tyrosinase. This study may provide reference foundation for the further study of the tyrosinase inhibitors, and also offer useful information for the comprehensive utilization of polyoxometalates.

Key words: tyrosinase, inhibitor, polyoxometalates, diphenolase activity

李莉莉, 陈丙年, 邓阳阳, 谢乐芳, 邢蕊, 王力. Dawson结构的多金属氧酸盐对酪氨酸酶的抑制作用[J]. 应用化学, 2017, 34(1): 83-89.

LI Lili, CHEN Bingnian, DENG Yangyang, XIE Lefang, XING Rui, WANG Li. Inhibitory Effects of Dawson Type Polyoxometalates on Tyrosinase[J]. Chinese Journal of Applied Chemistry, 2017, 34(1): 83-89.

参考文献

[1]	Jo Y H,Seo G U,Yuk H G,et al. Antioxidant and Tyrosinase Inhibitory Activities of Methanol Extracts from Magnolia Denudata and Magnolia Denudata Var. Purpurascens Flowers[J]. Food Res Int,2012,47(2):197-200.
[2]	Si Y X,Wang Z J,Park D,et al. Effect of Hesperetin on Tyrosinase:Inhibition Kinetics Integrated Computational Simulation Study[J]. Int J Biol Macromol,2012,50(1):257-262.
[3]	Komori Y,Imai M,Yamauchi T,et al. Effect of P-Aminophenols on Tyrosinase Activity[J]. Bioorg Med Chem,2014,22(15):3994-4000.
[4]	Si Y X,Ji S,Fang N Y,et al. Effects of Piperonylic Acid on Tyrosinase: Mixed-type Inhibition Kinetics and Computational Simulations[J]. Process Biochem,2013,48(11):1706-1714.
[5]	Xing R,Zheng A,Wang F,et al. Functionality Study of Na6PMo11FeO40 as a Mushroom Tyrosinase Inhibitor[J]. Food Chem,2015,175:292-299.
[6]	PEI Chaojun.Inhibitory Effects of Gartrodin on Tyrosinase and Melanogenesis[D]. Suzhou:Soochow University,2013(in Chinese). 裴超俊. 天麻素对酪氨酸酶的抑制作用及黑色素生成的影响[D]. 苏州:苏州大学,2013.
[7]	YANG Meihua,SHI Yan,LI Zhicong,et al. Inhibitory Effect of Protocatechuik Acid on Tyrosinase Acitivity and Melanin Content in Mouse Melanoma B16 Cell[J]. J Xiamen Univ(Nat Sci),2013,52(6):842-844(in Chinese). 杨美花,石艳,李智聪,等. 原儿茶酸对小鼠黑色素瘤 B16 细胞酪氨酸酶活力及黑色素生成的抑制效应[J]. 厦门大学学报(自然科学版),2013,52(6):842-844.
[8]	Lin L,Dong Y,Zhao H,et al. Comparative Evaluation of Rosmarinic Acid, Methyl Rosmarinate and Pedalitin Isolated from Rabdosia Serra(MAXIM.) HARA as Inhibitors of Tyrosinase and α-Glucosidase[J]. Food Chem,2011,129(3):884-889.
[9]	SONG Kangkang.Effects of Inhibitors on Tyrosinase and Their Regulation on Melanogenesis[D]. Xiamen:Xiamen University,2007(in Chinese). 宋康康. 抑制剂对酪氨酸酶的效应及其对黑色素生成调控的研究[D]. 厦门:厦门大学,2007.
[10]	Yu Z L,Zhang Z,Zeng W C.Investigation of Antibrowning Activity of Pine Needle(Cedrus Deodara) Extract with Fresh-cut Apple Slice Model and Identification of the Primary Active Components[J]. Eur Food Res Technol,2014,239(4):669-678.
[11]	Ha Y M,Kim J A,Park Y J,et al. Analogs of 5-(Substituted Benzylidene) Hydantoin as Inhibitors of Tyrosinase and Melanin Formation[J]. Biochim Biophys Acta-Gen Subj,2011,1810(6):612-619.
[12]	Anantharaman A,Hemachandran H,Priya R R,et al. Inhibitory Effect of Apocarotenoids on the Activity of Tyrosinase:Multi-spectroscopic and Docking Studies[J]. J Biosci Bioeng,2016,121(1):13-20.
[13]	Moudjahed M,Dermeche L,Benadji S,et al. Dawson-type Polyoxometalates as Green Catalysts for Adipic Acid Synthesis[J]. J Mol Catal A-Chem,2016,414:72-77.
[14]	Tang Q,Zhang C J,Zhang C H,et al. Two Sandwich-type Compounds from Keggin Polyoxometalate, d10 Metals and the Product of in Situ Catalyzed Decarboxylation of Pyrazine-2,3-dicarboxylic Acid[J]. Inorg Chem Commun,2012,15:238-242.
[15]	Xia L,Shuaishuai W,Changgen F.Synthesis and Anticancer Properties of Tungstosilicic Polyoxometalate Containing 5-Fluorouracil and Neodymium[J]. J Rare Earth,2010,28(6):965-968.
[16]	TAN Rongxin,CUI Shuxin,WANG Hui,et al. Syntheses and Antitumor Activities of Four Titanium-containing Polyoxometalate[J]. J Mol Sci,2013,29(2):152-155(in Chinese). 谭荣欣,崔术新,王慧,等. 4种含钛的多金属氧酸盐的合成及抗肿瘤活性研究[J]. 分子科学学报,2013,29(2):152-155.
[17]	GAN Qiang,LIU Xia,FENG Changgen.Research Progress on Antitumor Effect of Polyoxometalates[J]. Sci Technol Rev,2011,29(31):75-79(in Chinese). 甘强,刘霞,冯长根. 多金属氧酸盐抗肿瘤研究进展[J]. 科技导报,2011,29(31):75-79.
[18]	Yu X,Chen C,Peng J,et al. Antibacterial-active Multilayer Films Composed of Polyoxometalate and Methyl Violet:Fabrication, Characterization and Properties[J]. Thin Solid Films,2014,571:69-74.
[19]	CHEN Bingnian,FENG Zhenge,WANG Li.Antibacterial Activities of Polyoxometalates Containing Silicon[J]. Chem J Chinese Univ,2011,32(5):1033-1036(in Chinese). 陈丙年,冯珍鸽,王力. 含硅多金属氧酸盐的抑菌作用[J]. 高等学校化学学报,2011,32(5):1033-1036.
[20]	FENG Zhenge,CAI Huinong,WANG Li,et al. Antibacterial Activity of Polyoxometalates Containing Vanadium[J]. Chinese J Appl Chem,2010,27(8):990-992(in Chinese). 冯珍鸽,蔡慧农,王力,等. 含钒多金属氧酸盐的抑菌活性[J]. 应用化学,2010,27(8):990-992.
[21]	Lee S Y,Fiene A,Li W,et al. Polyoxometalates-potent and Selective Ecto-nucleotidase Inhibitors[J]. Biochem Pharmacol,2015,93(2):171-181.
[22]	ZHENG Aping,WANG Fang,XING Rui,et al. Functionality Research of Keggin-type Polyoxotungstate as Potent Mushroom Tyrosinase Inhibitors[J]. Chem J Chinese Univ,2014,35(3):476-481(in Chinese). 郑阿萍,王芳,邢蕊,等. 两种多酸型酪氨酸酶抑制剂的性能研究[J]. 高等学校化学学报,2014,35(3):476-481.
[23]	Xing R,Wang F,Dong L,et al. Inhibitory Effects of Na7PMo11CuO40 on Mushroom Tyrosinase and Melanin Formation and Its Antimicrobial Activities[J]. Food Chem,2016,197:205-211.
[24]	XING Rui,ZHENG Aping,WANG Fang,et al. The Inhibitory Mechanism Research of Vanadate-substituted Polyoxometalates on Tyrosinase[J]. J Mol Sci,2015,31(5):436-440(in Chinese). 邢蕊,郑阿萍,王芳,等. 钒取代的多酸盐对酪氨酸酶抑制机理的研究[J]. 分子科学学报,2015,31(5):436-440.
[25]	Jing S,Wang Z,Zhu W,et al. Oxidation of Cyclohexane with Hydrogen Peroxide Catalyzed by Dawson-type Vanadium-substituted Heteropolyacids[J]. React Kinet Catal Lett,2006,89(1):55-61.
[26]	GAO Lihua,ZHAO Yue,ZHAO Huizhen,et al. Studies on the Stability of Transtion Molybdophosphoric Heteropolyacids Having Dawson Structure[J]. J Harbin Normal Univ(Nat Sci),1993,9(2):52-56(in Chinese). 高丽华,赵月,赵慧珍,等. Dawson 结构钼磷过渡元素三元杂多酸稳定性的研究[J]. 哈尔滨师范大学学报(自然科学),1993,9(2):52-56.
[27]	Xie L P,Chen Q X,Huang H,et al. Inhibitory Effects of Cupferron on the Monophenolase and Diphenolase Activity of Mushroom Tyrosinase[J]. Int J Biochem Cell B,2003,35(12):1658-1666.
[28]	GOU Lin,LU Hang,WANG Xiyao,et al. Study of Sodium Thiosulfate on Tyrosinase Inhibition Effect[J]. J Xiamen Univ(Nat Sci),2014,53(2):263-266(in Chinese). 芶琳,卢航,王西瑶,等. 硫代硫酸钠对酪氨酸酶的抑制作用[J]. 厦门大学学报(自然科学版),2014,53(2):263-266.
[29]	Yin S J,Si Y X,Chen Y F,et al. Mixed-type Inhibition of Tyrosinase from Agaricus Bisporus by Terephthalic Acid:Computational Simulations and Kinetics[J]. Protein J,2011,30(4):273-280.
[30]	SONG Kangkang,QIU Ling,HUANG Huang,et al. The Inhibitory Effect of Tyrosinase by Arbutin as Cosmetic Additive[J]. J Xiamen Univ(Nat Sci),2004,42(6):791-794(in Chinese). 宋康康,邱凌,黄璜,等. 熊果甙作为化妆品添加剂对酪氨酸酶抑制作用[J]. 厦门大学学报(自然科学版),2004,42(6):791-794.
[31]	Hu X Y,Chen B N,Wang L,et al. Inhibition of α/β-K6P2W18O62·10H2O on the Activity of Mushroom Tyrosinase and Its Antimicrobial Effects[J]. Chem Res Chinese Univ,2012,28(5):862-865.
[32]	TENG Zhijun.Application Research and Preparation of Dawson Type Multicomponent Heteropoly Compounds[D]. Lanzhou:Lanzhou Jiaotong University,2010(in Chinese). 滕志君. Dawson型多金属氧酸盐催化剂的制备及其应用研究[D]. 兰州:兰州理工大学,2010.
[33]	Hu Y H,Liu X,Jia Y L,et al. Inhibitory Kinetics of Chlorocinnamic Acids on Mushroom Tyrosinase[J]. J Biosci Bioeng,2014,117(2):142-146.
[34]	Chai W M,Liu X,Hu Y H,et al. Antityrosinase and Antimicrobial Activities of Furfuryl Alcohol, Furfural and Furoic Acid[J]. Int J Biol Macromol,2013,57:151-155.
[35]	Lou S N,Yu M W,Ho C T.Tyrosinase Inhibitory Components of Immature Calamondin Peel[J]. Food Chem,2012,135(3):1091-1096.
[36]	Doğan S,Turan P,Doğan M,et al. Inhibition Kinetic and Mechanism of Polyphenol Oxidase from Various Sources by Diethyldithiocarbamic Acid[J]. Int J Food Sci Tech,2008,43(7):1316-1322.