3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin
• 英文别名: 3.4,5-trimethoxy-epicatechin-3-gallate；[(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trimethoxybenzoate
• 化学式: C₂₅H₂₄O₁₀
• 分子量: 484.46
• InChiKey: YWLGYHHJYFPEJD-DHIUTWEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin 在 酪氨酸酶 作用下， 生成 [1-(3,4-Dihydroxyphenyl)-1-oxo-3-(2,4,6-trihydroxyphenyl)propan-2-yl] 3,4,5-trimethoxybenzoate
  参考文献：
  名称：

  一对合成茶儿茶素衍生差向异构体的比较：黑色素瘤的合成，抗叶酸活性和酪氨酸酶介导的活化。

  摘要：

  尽管存在生物利用度问题，但由于茶儿茶素在多种动物模型中的功效，它们已成为有前途的化学预防剂。我们合成了两种儿茶素衍生的化合物3- O-（3,4,5-三甲氧基苯甲酰基）-（-）-儿茶素（TMCG）和3- O-（3,4,5-三甲氧基苯甲酰基）-（-）-表儿茶素（TMECG），旨在提高茶多酚的稳定性和细胞吸收性。在各种癌细胞系统中分析了这两种化合物的抗增殖和促凋亡活性，并且容易合成且产率高的TMCG在黑色素瘤和非黑色素瘤细胞系中的活性均高于TMECG。TMCG还是更好的二氢叶酸还原酶抑制剂，并被酪氨酸酶更有效地氧化，可能解释了这些差向异构体之间的活性差异。

  DOI：

  10.1002/cmdc.201000482
• 作为产物：
  描述：

  儿茶提取物 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 四丁基氯化铵 、 氢气 、 L-Selectride 、 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin
  参考文献：
  名称：

  Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins

  摘要：

  我们合成了新型茶儿茶素衍生物，并对这些衍生物和其他茶多酚结合二氢叶酸还原酶（DHFR）的能力进行了结构-活性研究。数据显示，所有分子都能与游离酶有效结合，而且合成化合物和天然类似物的解离常数相同。儿茶素结构的多酚比表儿茶素结构的多酚对 DHFR 的抑制效果更好。此外，还在培养的肿瘤细胞中研究了抗增殖活性，数据显示，儿茶素异构体的新型衍生物活性更高。酯键合没食子酸酯分子上带有羟基的衍生物与 DHFR 的体外结合力较高，但在细胞培养过程中，由于在生理 pH 值下会发生电离，因此会出现转运问题。研究还评估了儿茶素与血清白蛋白的结合对其生物活性的影响。本研究提供的信息对于设计从茶叶儿茶素中提取的新型药用活性化合物非常重要。数据表明，改变儿茶素的结构以避免与血清白蛋白的相互作用并促进质膜转运，对于儿茶素的细胞内功能至关重要。

  DOI：

  10.3390/molecules18078319

文献信息

• Antimicrobial Activity of 3-<i>O</i>-Acyl-(-)-epicatechin and 3-<i>O</i>-Acyl-(+)-catechin derivatives
  作者：Park, Ki Duk、Park, Yoon Sun、Cho, Sung Jin、Sun, Won Suck、Kim, Sung Han、Jung, Do Hyun、Kim, Jung Han

  DOI：10.1055/s-2004-818923

  日期：2004.3

  compounds, 3- O-acyl-(-)-epicatechins and 3- O-acyl-(+)-catechins possessing various aromatic groups and aliphatic chains of varying length from C4 to C16 for increasing lipophilicity were synthesized and tested for antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi. The (-)-epicatechin and (+)-catechin derivatives comprised of aromatic groups increased activity and derivatives

  作为抗菌促进化合物的探索性研究，3-O-酰基-（-）-表儿茶素和3-O-酰基-（+）-儿茶素具有不同的芳香族基团和从C4到C16的不同长度的脂族链，以增加亲脂性。合成并测试了对革兰氏阳性，革兰氏阴性细菌和真菌的抗菌活性。由芳族基团组成的（-）-表儿茶素和（+）-儿茶素衍生物的活性增强，并且在C8至C10的附近具有碳原子酰基链基的衍生物表现出很强的抗菌活性（MIC = 2-8 microg / ml）抵抗革兰氏阳性细菌，抗真菌活性弱。然而，当取代基的碳链长度太短（C4至C6）或太长（C16）时，活性降低。
• Anticancer activity of 3-O-acyl and alkyl-(−)-epicatechin derivatives
  作者：Ki Duk Park、Sul Gi Lee、Sung Uk Kim、Sung Han Kim、Won Suck Sun、Sung Jin Cho、Do Hyeon Jeong

  DOI：10.1016/j.bmcl.2004.07.063

  日期：2004.10

  By changing the structure or replacing the gallate group of (-)-ECG, 3-O-acyl and alkyl-(-)-epicatechin derivatives were synthesized to be screen as anticancer agents using the MTT assay in vitro against cancer cell lines (PC3, SKOV3, U373MG). 3-O-Acyl and alkyl-(-)-epicatechin derivatives (4-25) exhibited better anticancer activity than (-)-ECG and specially, compounds 6-8, 17-19, which were modified aliphatic chains with moderate sizes (C8-C12) showed strong anticancer activity (IC50 = 6.4-31.2 muM). The introduction of an alkyloxy group on 3-O-hydroxyl instead of an acyloxy group significantly enhanced inhibitory activity. Consequently, the compound that showed the most potency as anticancer agents were 3-O-decyl-(-)-epicatechin (18) (IC50 = 8.9, 7.9, 6.4 muM against PC3, SKOV3, U373MG, respectively), which modified the appropriate lipophilic group on the C-3 hydroxyl as an alkyloxy group. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Activity of a 3,4,5-Trimethoxybenzoyl Ester Analogue of Epicatechin-3-gallate
  作者：Luís Sánchez-del-Campo、Francisco Otón、Alberto Tárraga、Juan Cabezas-Herrera、Soledad Chazarra、José Neptuno Rodríguez-López

  DOI：10.1021/jm701346h

  日期：2008.4.1

  Despite presenting bioavailability problems, tea catechins have emerged as promising chemopreventive agents because of their observed efficacy in various animal models. To improve the stability and cellular absorption of tea polyphenols, we developed a new catechin-derived compound, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), which has shown significant antiproliferative activity against several cancer cell lines, especially melanoma. The presence of methoxy groups in its ester-bound gaily] moiety drastically decreased its antioxidant and prooxidant properties without affecting its cell-antiproliferative effects, and the data indicated that the 3-gallyl moiety was essential for its biological activity. As regards its action mechanism, we demonstrated that TMECG binds efficiently to human dihydrofolate reductase and down-regulates folate cycle gene expression in melanoma cells. Disruption of the folate cycle by TMECG is a plausible explanation for its observed biological effects and suggests that, like other antifolate compounds, TMECG could be of clinical value in cancer therapy.
• ANTIFOLATE COMPOUNDS FOR THE TREATMENT OF MELANOMA
  申请人：Universidad de Murcia

  公开号：EP2231151B1

  公开（公告）日：2013-08-28
• COMBINATIONS (CATECHINS AND METHOTREXATE) FOR USE IN THE TREATMENT OF MELANOMAS
  申请人：UNIVERSIDAD DE MURCIA

  公开号：US20150231109A1

  公开（公告）日：2015-08-20

  The invention provides a method of treatment of melanoma comprising administering a tyrosinase expression enhancer, such as MTX, and a tyrosinase-activated prodrug, such as TMECG or TMCG, to an individual in need thereof. Also provided is a method of treating melanoma comprising administering a tyrosinase-activated prodrug and a compound for differentiating a stem-like tumor cell into a matured cell that is a tyrosinase producer to an individual in need thereof. Further provided is a method of treatment of melanoma comprising administering a tyrosinase expression enhancer and a tyrosinase-activated prodrug to an individual in need thereof, wherein the individual has a melanoma in which one or more of BRAF, NRAS, p53, GNAQ, EGFR, PDGFR, RAC or c-kit carries a mutation.