山奈酚葡萄糖醛酸苷 | 22688-78-4

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 山奈酚葡萄糖醛酸苷
• 中文别名: 山奈酚3葡糖苷酸
• 英文名称: kaempferol 3-O-β-D-glucuronide
• 英文别名: Kaempferol 3-glucuronide；kaempferol 3-O-β-D-glucopyranosiduronic acid；kaempferol 3-O-β-D-glucoronopyranoside；kaempferol 3-O-β-D-glucuronopyranoside；3-O-β-D-glucuronopyranosyl kaempferol；kaempferol 3-O-(β-D-glucoronide)；(2S,3S,4S,5R,6S)-6-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 22688-78-4
• 化学式: C₂₁H₁₈O₁₂
• 分子量: 462.367
• InChiKey: FNTJVYCFNVUBOL-ZUGPOPFOSA-N

物化性质

• 熔点：
  189-191 °C
• 沸点：
  876.8±65.0 °C(Predicted)
• 密度：
  1.87
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  2.300 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  203
• 氢给体数：
  7
• 氢受体数：
  12

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38

制备方法与用途

生物活性 Kaempferol 3-O-β-D-glucuronide（山奈酚-3-葡萄糖苷）是一种结合代谢产物，具有显著的抗炎作用。它能够显著抑制多种促炎介质，如 IL-1β、NO、PGE2 和 LTB4，并上调抗炎细胞因子 IL-10 的分泌。

靶点

IL-1β
IL-10

反应信息

• 作为反应物：
  描述：

  山奈酚葡萄糖醛酸苷 在 盐酸 、 甲醇 作用下， 反应 2.0h， 以100%的产率得到山奈酚
  参考文献：
  名称：

  Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

  摘要：

  发现，几种天然药材和药用食品的甲醇提取物对大鼠晶状体醛糖还原酶显示抑制作用。在大多数情况下，通过生物测定指导的分离方法，分离得到黄酮类化合物作为活性成分，其中，槲皮苷（IC50=0.15 μM）、愈创木脂苷（0.18 μM）和去甲基芸香糖苷-1（0.082 μM）显示出强的抑制活性。去甲基芸香糖苷-1显示了最强的活性，相当于商品化合成醛糖还原酶抑制剂依帕司他（0.072 μM）的活性。为了阐明黄酮类化合物对醛糖还原酶抑制活性的结构要求，检测了各种黄酮类化合物及相关化合物。结果表明，黄酮类化合物的以下结构要求是：1）具有7-羟基和/或邻苯二酚结构的黄酮和黄酮醇（在B环上的3′,4′-二羟基结构）显示出强的活性；2）5-羟基结构并不影响活性；3）3-羟基和7-O-葡糖基结构降低活性；4）2-3双键增强活性；5）具有邻苯二酚结构的黄酮和黄酮醇显示出比具有连苯三酚结构（3′,4′,5′-三羟基结构）的化合物更强的活性。

  DOI：

  10.1248/cpb.50.788
• 作为产物：
  描述：

  kaempferol 3-O-β-D-glucuronide 6''-ethyl ester 在 盐酸 作用下， 反应 0.05h， 生成 山奈酚葡萄糖醛酸苷
  参考文献：
  名称：

  柽柳花的黄酮类化合物

  摘要：

  摘要 山柰酚 3-O-β-D-葡萄糖醛酸乙酯、槲皮素 3-O-β-D-葡萄糖醛酸甲酯和乙酯已从柽柳花的丙酮水溶液提取物中分离得到。此外，山奈酚 3-O-sulphate-7,4'-二甲醚和游离苷元被分离出来。通过常规方法、FAB-MS和13C NMR光谱测量确定结构。

  DOI：

  10.1016/s0031-9422(00)80549-x

文献信息

• Regioselective Glucuronidation of Flavonols by Six Human UGT1A Isoforms
  作者：Baojian Wu、Beibei Xu、Ming Hu

  DOI：10.1007/s11095-011-0418-5

  日期：2011.8

  Glucuronidation is a major barrier to flavonoid bioavailability; understanding its regiospecificity and reaction kinetics would greatly enhance our ability to model and predict flavonoid disposition. We aimed to determine the regioselective glucuronidation of four model flavonols using six expressed human UGT1A isoforms (UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10). In vitro reaction kinetic profiles of six UGT1A-mediated metabolism of four flavonols (all with 7-OH group) were characterized; kinetic parameters (Km, Vmax and CLint = Vmax/Km) were determined. UGT1A1 and 1A3 regioselectively metabolized the 7-OH group, whereas UGT1A7, 1A8, 1A9 and 1A10 preferred to glucuronidate the 3-OH group. UGT1A1 and 1A9 were the most efficient conjugating enzymes with Km values of ≤1 μM and relative catalytic efficiency ratios of ≥5.5. Glucuronidation by UGT1As displayed surprisingly strong substrate inhibition. In particular, Ksi values (substrate inhibition constant) were less than 5.4 μM for UGT1A1-mediated metabolism. UGT1A isoforms displayed distinct positional preferences between 3-OH and 7-OH of flavonols. Differentiated kinetic properties between 3-O- and 7-O- glucuronidation suggested that (at least) two distinct binding modes within the catalytic domain were possible. The existence of multiple binding modes should provide better “expert” knowledge to model and predict UGT1A-mediated glucuronidation.

  葡萄糖醛酸化是类黄酮生物利用度的主要障碍；了解其区域选择性和反应动力学会大大增强我们建模和预测类黄酮处置的能力。我们的目标是确定四种模型二苯乙烯酮在六种表达的人类UGT1A同工酶（UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10）作用下的区域选择性葡萄糖醛酸化。表征了六种UGT1A介导的四种二苯乙烯酮（均含7-OH基团）的体外反应动力学曲线；确定了动力学参数（Km, Vmax和CLint = Vmax/Km）。UGT1A1和1A3区域选择性地代谢7-OH基团，而UGT1A7, 1A8, 1A9和1A10更倾向于对3-OH基团进行葡萄糖醛酸化。UGT1A1和1A9是最有效的结合酶，其Km值≤1 μM，相对催化效率比≥5.5。UGT1A的葡萄糖醛酸化显示出惊人的强底物抑制作用。特别是，UGT1A1介导的代谢的Ksi值（底物抑制常数）小于5.4 μM。UGT1A同工酶显示出对二苯乙烯酮的3-OH和7-OH的不同位置偏好。3-O-和7-O-葡萄糖醛酸化的区分动力学特性表明（至少）催化域内存在两种不同的结合模式。多种结合模式的存在应提供更好的“专家”知识来建模和预测UGT1A介导的葡萄糖醛酸化。
• 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。
• The Anti-thrombotic Active Constituents from Centella asiatica
  作者：Toshiko Satake、Kohei Kamiya、Yin An、Tomomi Oishi(nee Taka)、Junichiro Yamamoto

  DOI：10.1248/bpb.30.935

  日期：——

  The in vitro effects of a methanol extract from the aerial parts of Centella asiatica on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. 3,5-Di-O-caffeoyl quinic acid, 1,5-di-O-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, and chlorogenic acid, together with asiaticoside, kaempferol, quercetine, kaempferol-3-O-β-D-glucoside and quercetin-3-O-β-D-glucoside were all isolated from the methanol extract. Amongst these, only 3,5-di-O-caffeoylquinic acid showed significant inhibition of shear-induced platelet activation and dynamic coagulation. The reactive curve of the inhibitory effect on the platelet reaction and the dynamic coagulation showed a bell-shape.

  大鼠口服积雪草气生部分的甲醇提取物后，通过对无抗凝血的血液进行止血测定，评估了该提取物对剪切力诱导的血小板活化和凝血的体外效应。3,5-二-O-咖啡酰基奎宁酸、1,5-二-O-咖啡酰基奎宁酸、3,4-二-O-咖啡酰基奎宁酸、4,5-二-O-咖啡酰基奎宁酸、绿原酸以及积雪草苷、从甲醇提取物中分离出了山柰酚、槲皮素、山柰-3-O-β-<小>D-葡萄糖苷和槲皮素-3-O-β-<小>D-葡萄糖苷。其中，只有 3,5-二-O-咖啡酰奎宁酸对剪切力诱导的血小板活化和动态凝血有明显的抑制作用。对血小板反应和动态凝血抑制作用的反应曲线呈钟形。
• Flavonol glycosides of Euphorbia retusa and E. sanctae-catharinae
  作者：Nabiel A.M. Saleh

  DOI：10.1016/s0031-9422(00)83562-1

  日期：1985.2
• USE OF FLAVONOIDE COMPOUNDS FOR THE PROPHYLAXIS AND THERAPY OF ISCHAEMIC OR INFLAMMATORY HEART AND CARDIOVASCULAR DISEASES
  申请人：Esperester Anke

  公开号：US20110053874A1

  公开（公告）日：2011-03-03

  The present invention relates to the use of flavonoid compounds, particularly quercetin-3-O-β-D-glucuronide and kaempferol-3-O-β-D-glucuronide and their glucosides, for preventing diseases of the heart. Red vine leaf extract has proved a particularly advantageous source of the flavonoid compounds in question.