3-O-(4-hydroxy-3,5-dimethoxybenzoyl)epicatechin

• 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-(4-hydroxy-3,5-dimethoxybenzoyl)epicatechin
• 英文别名: 2R,3R-epicatechin 3-(3,5-di-O-methyl)gallate；lysidicichin；[(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 4-hydroxy-3,5-dimethoxybenzoate
• 化学式: C₂₄H₂₂O₁₀
• 分子量: 470.433
• InChiKey: LMXVAQGQBWGDQE-FYYLOGMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 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-(4-hydroxy-3,5-dimethoxybenzoyl)epicatechin
  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

• ANTIFOLATE COMPOUNDS FOR THE TREATMENT OF MELANOMA
  申请人：Rodriguez-Lopez Jose Neptuno

  公开号：US20100279971A1

  公开（公告）日：2010-11-04

  This invention relates to compounds of the formula X) or XI) (X) (XI) wherein: each —R 1 , —R 2 and —R 3 is independently -Q 1 , —OH or —H, where at least one of —R 1 , —R 2 and —R 3 is not —H or —OH; each —R 4 and —R 5 is independently -Q 2 or —H; each -Q 1 is independently selected from: —F, —Cl, —R A , —OR A , —SH, —SR A , where each —R A is independently selected from methyl and ethyl, which may substituted by one or more fluoro or chloro groups; and each -Q 2 is selected from: —F, —Cl, —R B , —OR B , —SH, —SR B , where each —R B is independently selected from methyl and ethyl, which may substituted by one or more fluoro or chloro groups; which are useful in the treatment of melanoma.
• 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.
• US9060997B2
  申请人：——

  公开号：US9060997B2

  公开（公告）日：2015-06-23
• Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
  作者：Magalí Sáez-Ayala、María Fernández-Pérez、Soledad Chazarra、Nani Mchedlishvili、Alberto Tárraga-Tomás、José Rodríguez-López

  DOI：10.3390/molecules18078319

  日期：——

  Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

  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。