EGCG衍生物合成及药理活性研究进展

doi:10.13305/j.cnki.jts.2016.02.002

摘要/Abstract

摘要： 表没食子儿茶素没食子酸酯（EGCG）是茶叶中一类重要儿茶素, 在体外细胞实验及动物体内实验中,表现出多种生物活性。但EGCG的“多羟基”的化学结构具有脂溶性差,生物利用率低以及稳定性差等缺点,影响其被深度利用,而分子修饰能显著的改善EGCG多种理化性质。本文综述了最近国内外EGCG结构修饰的常见方法,合成过程以及相应的药理活性研究,以期为后续EGCG的进一步研究提供参考。

关键词: EGCG, 分子修饰, 衍生物, 进展, 生物活性

Abstract: (-)-Epigallocatechin-3-gallate (EGCG), one of the important catechins in tea, has efficient bioactivity of cell experiment in vitro and animal models in vivo. However, it was not being fully utilized because of the disadvantages of poor liposolubility and stability, as well as low bioavailability, which was resulted from its ‘polyhydroxy’ chemical structure. Excitingly, the molecular modification would be used to improve the physicochemical character of EGCG. This review will summarize the methods on molecular modification of EGCG and investigation of biological activities, which hopes to provide worthful references to the further study of EGCG.

Key words: EGCG, molecular modification, derivatives, review, bioactivity

中图分类号:

柳敏, 饶国武, 华允芬. EGCG衍生物合成及药理活性研究进展[J]. 茶叶科学, 2016, 36(2): 119-130. doi: 10.13305/j.cnki.jts.2016.02.002.

LIU Min, RAO Guowu, HUA Yunfen. Research Advance in Synthesis and Pharmacological Effects of EGCG Derivatives[J]. Journal of Tea Science, 2016, 36(2): 119-130. doi: 10.13305/j.cnki.jts.2016.02.002.

参考文献

[1] Osanai K, Huo C, Landis-Piwowar K R, et al. Synthesis of (2R, 3R)-epigallocatechin-3-O-(4-hydroxybenzoate), a novel catechin from Cistus salvifolius, and evaluation of its proteasome inhibitory activities[J]. Tetrahedron, 2007, 63(32): 7565-7570.
[2] Karori S, Wachira F, Wanyoko J, et al.Antioxidant capacity of different types of tea products[J]. African Journal of Biotechnology, 2007, 6(19): 2287-2296.
[3] Zheng R, Chen TS, Lu TA comparative reverse docking strategy to identify potential antineoplastic targets of tea functional components and binding mode[J]. International journal of molecular sciences, 2011, 12(8): 5200-5212.
[4] Cichello S, Liu P, Jois M.The anti-obesity effects of EGCG in relation to oxidative stress and air-pollution in China[J]. Natural products and bioprospecting, 2013, 3(6): 256-266.
[5] Zhang Y, Wang SX, Ma JW, et al.EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of p-glycoprotein inhibition[J]. Journal of Neuro-Oncology, 2014, 121(1): 1-12.
[6] An Z, Qi Y, Huang D, et al.EGCG inhibits Cd²+-induced apoptosis through scavenging ROS rather than chelating Cd²+ in HL-7702 cells[J]. Toxicology mechanisms and methods, 2014, 24(4): 259-267.
[7] Landis-Piwowar K, Bazzi S, Dou QP.Discovery of green tea polyphenol-based proteasome inhibitors—A successful collaboration with Tak-Hang (Bill) Chan[J]. Canadian Journal of Chemistry, 2011, 90(1): 17-22.
[8] Yanase E, Matsumoto E, Shinoda Y.Synthesis of methyl derivatives of epigallocatechin gallate (EGCg) and their stabilities[J]. ITE Letters on Batteries New Technologies & Medicine (with News), 2005, 6(1): 34-37.
[9] Mori S, Miyake S, Kobe T, et al.Enhanced anti-influenza a virus activity of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives: Effect of alkyl chain length[J]. Bioorganic & medicinal chemistry letters, 2008, 18(14): 4249-4252.
[10] Moon Y-H, Lee J-H, Ahn J-S, et al.Synthesis, structure analyses, and characterization of novel epigallocatechin gallate (EGCG) glycosides using the glucansucrase from Leuconostoc mesenteroides B-1299CB[J]. Journal of agricultural and food chemistry, 2006, 54(4): 1230-1237.
[11] Lin S F, Lin Y-H, Lin M, et al.Synthesis and structure-activity relationship of 3-O-acylated (-)-epigallocatechins as 5α-reductase inhibitors[J]. European journal of medicinal chemistry, 2010, 45(12): 6068-6076.
[12] Fudouji R, Tanaka T, Taguri T, et al.Coupling reactions of catechins with natural aldehydes and allyl alcohols and radical scavenging activities of the triglyceride-soluble products[J]. Journal of Agricultural and Food Chemistry, 2009, 57(14): 6417-6424.
[13] Lam W H, Kazi A, Kuhn D J, et al.A potential prodrug for a green tea polyphenol proteasome inhibitor: evaluation of the peracetate ester of (-)-epigallocatechin gallate [(-)-EGCG][J]. Bioorganic & Medicinal Chemistry, 2004, 12(21): 5587-5593.
[14] Saijo R.Isolation and chemical structures of two new catechins from fresh tea leaf[J]. Agricultural and Biological Chemistry, 1982, 46(7): 1969-1970.
[15] Forester SC, Lambert JD.The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice[J]. Journal of Functional Foods, 2015, 17: 183-188.
[16] 赵新. 甲基化EGCG对SGC7901细胞Cyclin E、Bcl-2、Bcl-xL表达影响与抑癌作用研究[J]. 现代肿瘤医学, 2012, 20(1): 51-55.
[17] MIYASE T, SANO M. Preparation of catechin derivatives with increased stability: JP2001253879 [P].2001-09-18.
[18] Meng X, Sang S, Zhu N, et al.Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats[J]. Chemical Research in Toxicology, 2002, 15(8): 1042-1050.
[19] 吕海鹏, 孙业良, 林智, 等. 表没食子儿茶素没食子酸酯的甲基化分子修饰[J]. 食品科学, 2010(15): 139-142.
[20] 伍妍俊, 汪小钢, 宛晓春. 甲基化EGCG的合成及其在人工模拟胃肠液中的稳定性[J]. 安徽农业大学学报, 2010, 37(4): 688-691.
[21] Utenova BT, Malterud KE, Rise F.Antioxidant activity of O-protected derivatives of (-)-epigallocatechin-3-gallate: inhibition of soybean and rabbit 15-lipoxygenases[J]. Arkivoc, 2007, 40(6): 6-16.
[22] 王保超. 甲基化EGCG类似物的设计合成及抗肿瘤MDR活性研究[D]. 上海: 中国海洋大学, 2014.
[23] Aihara Y, Yoshida A, Furuta T, et al.Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group[J]. Bioorganic & Medicinal Chemistry Letters, 2009, 19(15): 4171-4174.
[24] Wan SB, Dou QP, Chan TH.Regiospecific and enantioselective synthesis of methylated metabolites of tea catechins[J]. Tetrahedron, 2006, 62(25): 5897-5904.
[25] 费冬梅. 甲基化EGCG 的酶法合成研究[D]. 杭州: 中国农业科学院茶叶研究所, 2011.
[26] 朱松. 表没食子儿茶素没食子酸酯(EGCG)酶法乙酰化分子修饰及其产物的抗氧化性能研究[D]. 无锡: 江南大学, 2014.
[27] 沈生荣, 金超芳. 儿茶素的分子修饰[J]. 茶叶, 1999, 25(2): 76-79.
[28] 陈平, 孙东, 郑小明. EGCG棕榈酸酯的制备, 结构及其抗氧化活性[J]. 浙江大学学报: 理学版, 2003, 30(4): 422-425.
[29] 孙东, 陈平. EGCG肉豆蔻酸酯的制备, 结构及其抗氧化活性[J]. 温州医学院学报, 2006, 36(3): 225-227.
[30] 陈平. 抗氧化剂的EGCG脂肪酸酯及其制备方法: CN1448395[P].2003-10-15.
[31] 朱媛, 张雪松, 黄小忠. 脂溶性茶多酚制备工艺的研究[J]. 中国粮油学报, 2014(6): 74-78.
[32] Kuhn D, Lam W H, Kazi A, et al.Synthetic peracetate tea polyphenols as potent proteasome inhibitors and apoptosis inducers in human cancer cells[J]. Front Biosci, 2005, 10(2): 1010-1023.
[33] Matsumura K, Kaihatsu K, Mori S, et al.Enhanced antitumor activities of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives in vitro and in vivo[J]. Biochemical and biophysical research communications, 2008, 377(4): 1118-1122.
[34] Spencer J P.Metabolism of tea flavonoids in the gastrointestinal tract[J]. The Journal of nutrition, 2003, 133(10): 3255S-3261S.
[35] 陈义. 表没食子儿茶素没食子酸酯的富集提取、分离与改性[D]. 合肥: 安徽农业大学, 2007.
[36] Hyun E K, Park H Y, Kim H J, et al.Production of epigallocatechin gallate 7-O-α-d-Glucopyranoside (EGCG-G1) using the glucosyltransferase from leuconostoc mesenteroides[J]. Biotechnology progress, 2007, 23(5): 1082-1086.
[37] Kitao S, Ariga T, Matsudo T, et al.The syntheses of catechin-glucosides by transglycosylation with Leuconostoc mesenteroides sucrose phosphorylase[J]. Bioscience, biotechnology, and biochemistry, 1993, 57(12): 2010-2015.
[38] Osanai K, Landis-Piwowar K R, Dou Q P, et al. A para-amino substituent on the D-ring of green tea polyphenol epigallocatechin-3-gallate as a novel proteasome inhibitor and cancer cell apoptosis inducer[J]. Bioorganic & medicinal chemistry, 2007, 15(15): 5076-5082.
[39] Yu Z, Qin X L, Gu Y Y, et al.Prodrugs of fluoro-substituted benzoates of EGC as tumor cellular proteasome inhibitors and apoptosis inducers[J]. International journal of molecular sciences, 2008, 9(6): 951-961.
[40] M Koizumi,T Akao,L Imamura, et al.Enzymatic sulfation of isoamyl gallate and (-)-epigallocatechin gallate by bacterial arylsulfotransferase[J]. Chemical and pharmaceutical bulletin, 1992, 40(7): 1864-1867.
[41] Kumagai A, Nagaoka Y, Obayashi T, et al.Tumor chemopreventive activity of 3-O-acylated (-)-epigallocatechins[J]. Bioorganic & medicinal chemistry, 2003, 11(23): 5143-5148.
[42] Tobiason F L.Mndo and am1 molecular orbital and molecular mechanics analyses of (+)-catechin, (-)-epicatechin, and their 3-O-Acetyl derivatives[M]//Richard W Hemingway, Peter E Laks. Plant Polyphenols: Volume 59 of the series Basic Life Sciences. US: Springer, 1992: 459-478.
[43] Song J M, Park K D, Lee K H, et al.Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives[J]. Antiviral research, 2007, 76(2): 178-185.
[44] Furuta T, Hirooka Y, Abe A, et al.Concise synthesis of dideoxy-epigallocatechin gallate (DO-EGCG) and evaluation of its anti-influenza virus activity[J]. Bioorganic & medicinal chemistry letters, 2007, 17(11): 3095-3098.
[45] Uesato S, Taniuchi K, Kumagai A, et al.Inhibitory effects of 3-O-acyl-(+)-catechins on epstein-barr virus activation[J]. Chemical and Pharmaceutical Bulletin, 2003, 51(12): 1448-1450.
[46] Sakai M, Suzuki M, Nanjo F, et al. 3-O-acylated catechins and methods of producing same: EP19940104887 [P].1994-10-05[2015-09-30].
[47] Tanaka T, Kusano R, Kouno I.Synthesis and antioxidant activity of novel amphipathic derivatives of tea polyphenol[J]. Bioorganic & medicinal chemistry letters, 1998, 8(14): 1801-1806.
[48] Nakai M, Fukui Y, Asami S. Epigallocatechin dimers or trimers having lipase inhibitory activity and/or antioxidant activity: 20110124887 [P].2011-05-26.
[49] Siddiqui I A, Adhami V M, Bharali D J, et al.Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate[J]. Cancer Research, 2009, 69(5): 1712-1716.
[50] Folch-Cano C, Guerrero J, Speisky H, et al.NMR and molecular fluorescence spectroscopic study of the structure and thermodynamic parameters of EGCG/β-cyclodextrin inclusion complexes with potential antioxidant activity[J]. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2014, 78(1/4): 287-298.
[51] 张润华, 王贤和, 陈萍, 等. 表没食子儿茶素没食子酸酯增强食管癌细胞对阿霉素化疗敏感性[J]. 中华临床医师杂志: 电子版, 2013, 7(22): 10144-10147.