3-Hydroxyflavone glucuronide | 905840-93-9

• 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-Hydroxyflavone glucuronide
• 英文别名: flavonyl β-D-glucopyranosiduronic acid
• CAS: 905840-93-9
• 化学式: C₂₁H₁₈O₉
• 分子量: 414.369
• InChiKey: VEKBKNOLQIUOFC-ZUGPOPFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.73
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  146.66
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  methyl (flavonyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid)uronate 在 水 、 lithium hydroxide 作用下， 反应 28.0h， 以92%的产率得到3-Hydroxyflavone glucuronide
  参考文献：
  名称：

  4'-取代基对基于黄酮醇的 β-糖苷酶活性荧光指示剂效率的影响。

  摘要：

  本文介绍了基于激发态分子内质子转移 (ESIPT) 现象和黄酮醇对特定糖苷酶的作用敏感的新型荧光探针。使用各种方法合成 4'-取代的黄酮醇，并用D-葡萄糖、N-乙酰基-D-葡萄糖胺和D-葡萄糖醛酸。β-糖苷酶活性的评估在中性和酸性 pH 值下进行。在所有检查的情况下，酸性环境加速了酶水解。已经证明，在中性和酸性 pH 值下，所有测试糖的 4'-氯黄酮苷对水解酶的存在最敏感。反过来，4'-二甲基氨基黄酮基葡糖苷对葡糖苷酶的作用完全不敏感。通常，酶水解的速率随着 4'-取代基的吸电子性质的增加而增加。一个例外是三氟甲基，尽管它具有最有利的哈米特常数，但对提高其葡糖苷的水解速率的贡献不足。

  DOI：

  10.1039/d0ob01505a

文献信息

• Three-Dimensional Quantitative Structure-Activity Relationship Studies on UGT1A9-Mediated 3-O-Glucuronidation of Natural Flavonols Using a Pharmacophore-Based Comparative Molecular Field Analysis Model
  作者：Baojian Wu、John Kenneth Morrow、Rashim Singh、Shuxing Zhang、Ming Hu

  DOI：10.1124/jpet.110.175356

  日期：2011.2

  Glucuronidation is often recognized as one of the rate-determining factors that limit the bioavailability of flavonols. Hence, design and synthesis of more bioavailable flavonols would benefit from the establishment of predictive models of glucuronidation using kinetic parameters [e.g., K m, V max, intrinsic clearance (CLint) = V max/ K m] derived for flavonols. This article aims to construct position (3-OH)-specific comparative molecular field analysis (CoMFA) models to describe UDP-glucuronosyltransferase (UGT) 1A9-mediated glucuronidation of flavonols, which can be used to design poor UGT1A9 substrates. The kinetics of recombinant UGT1A9-mediated 3-O-glucuronidation of 30 flavonols was characterized, and kinetic parameters ( K m, V max, CLint) were obtained. The observed K m, V max, and CLint values of 3-O-glucuronidation ranged from 0.04 to 0.68 μM, 0.04 to 12.95 nmol/mg/min, and 0.06 to 109.60 ml/mg/min, respectively. To model UGT1A9-mediated glucuronidation, 30 flavonols were split into the training (23 compounds) and test (7 compounds) sets. These flavonols were then aligned by mapping the flavonols to specific common feature pharmacophores, which were used to construct CoMFA models of V max and CLint, respectively. The derived CoMFA models possessed good internal and external consistency and showed statistical significance and substantive predictive abilities ( V max model: q 2 = 0.738, r 2 = 0.976, r pred2 = 0.735; CLint model: q 2 = 0.561, r 2 = 0.938, rpred2 = 0.630). The contour maps derived from CoMFA modeling clearly indicate structural characteristics associated with rapid or slow 3-O-glucuronidation. In conclusion, the approach of coupling CoMFA analysis with a pharmacophore-based structural alignment is viable for constructing a predictive model for regiospecific glucuronidation rates of flavonols by UGT1A9.

  葡糖醛酸化通常被认为是限制类黄酮醇生物利用度的决定速率的因素之一。因此，利用类黄酮醇的动力学参数（如 Km、Vmax、内在清除率（CLint）= Vmax/ Km）建立葡糖醛酸化的预测模型，将有利于设计合成更多生物可利用的类黄酮醇。本文旨在构建针对3-OH位点的特定比较分子场分析（CoMFA）模型，描述UDP-葡糖醛酸基转移酶（UGT）1A9介导的类黄酮醇葡糖醛酸化过程，该模型可用于设计不佳的UGT1A9底物。我们对重组UGT1A9介导的30种类黄酮醇的3-O-葡糖醛酸化动力学进行了表征，并获得了动力学参数（Km、Vmax、CLint）。观察到的3-O-葡糖醛酸化Km、Vmax和CLint值分别在0.04至0.68 μM、0.04至12.95 nmol/mg/min和0.06至109.60 ml/mg/min之间。为了模拟UGT1A9介导的葡糖醛酸化，我们将30种类黄酮醇分为训练集（23个化合物）和测试集（7个化合物）。然后通过将类黄酮醇映射到特定的共同特征药效团来对齐，从而构建了Vmax和CLint的CoMFA模型。得到的CoMFA模型具有良好的内在和外在一致性，显示出统计学意义和实质性的预测能力（Vmax模型：q2 = 0.738，r2 = 0.976，rpred2 = 0.735；CLint模型：q2 = 0.561，r2 = 0.938，rpred2 = 0.630）。从CoMFA建模得到的轮廓图清晰地表明了与快速或慢速3-O-葡糖醛酸化相关的结构特征。总之，结合CoMFA分析和基于药效团的结构对齐方法是可行的，可以构建用于UGT1A9介导的类黄酮醇区域特异性葡糖醛酸化速率的预测模型。