4’,6,7-三羟异黄酮 | 17817-31-1

• 物质功能分类: 生物化工 - 提取物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 中文名称: 4’,6,7-三羟异黄酮
• 中文别名: 6,7-二羟基-3-(4-羟基苯基)-4H-苯并吡喃-4-酮；4',6,7-三羟异黄酮；4',6,7-三羟基异黄酮；6,7,4'-三羟基异黄酮
• 英文名称: 6,7,4'-trihydroxyisoflavone
• 英文别名: 6,7,4'-trihydroxyisoflavon；6,7,4’-trihydroxyisoflavone；6,7,4′-trihydroxyisoflavone；6,7,4'-trihydroxyisoflavanone；4',6,7,-trihydroxyisoflavone；4',6,7-trihydroxy-isoflavone；6,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one
• CAS: 17817-31-1
• 化学式: C₁₅H₁₀O₅
• 分子量: 270.241
• InChiKey: GYLUFQJZYAJQDI-UHFFFAOYSA-N

物化性质

• 熔点：
  >280℃
• 沸点：
  587.1±50.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基甲酰胺
• LogP：
  2.170 (est)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 海关编码：
  2914501900
• 安全说明：
  S22,S24/25
• 储存条件：
  室温

制备方法与用途

生物活性

Desmethylglycitein（4',6,7-三羟基异黄酮），是大豆苷元的代谢产物，来源于大豆(Glycine max)，具有抗氧化性和抗癌活性。Desmethylglycitein 在体内直接结合 CDK1 和 CDK2，抑制这两种激酶的活性。同时，它也是蛋白激酶 C (PKC)α 的直接抑制剂，在正常人皮肤成纤维细胞中，能够抑制太阳紫外线 (sUV) 诱导的基质金属蛋白酶1 (MMP1) 表达。此外，Desmethylglycitein 还以 ATP 竞争方式与细胞质中的 PI3K 结合，从而抑制 PI3K 和下游信号级联的活性，进而抑制 3T3-L1 前脂肪细胞中的脂肪形成。

靶点

• CDK1
• CDK2
• PKC

体外研究

Desmethylglycitein（4',6,7-三羟基异黄酮）以剂量和时间依赖性的方式抑制 HCT-116 和 DLD1 细胞的附着依赖性和非依赖性生长，且无细胞毒性。它在剂量依赖性的条件下抑制 CDK1 活性，并在 HCT-116 细胞中抑制 CDK2 的活性。Desmethylglycitein 使 HCT-116 细胞的周期停滞在 S 和 G2/M 期，处理浓度为 100 μM 的 6,7,4′-THIF 组中处于 S 期细胞的比例较高（29.5% 对比 19.1%）。

细胞活力测定

• 细胞系：HCT-116 细胞
• 浓度：0，12.5，25，50 或 100 μM
• 孵育时间：24，48 或 72 小时
• 结果：抑制 HCT-116 细胞的附着依赖性和非依赖性生长。

蛋白质印迹分析

• 细胞系：HCT-116 和 DLD1 细胞
• 浓度：0，25，50 或 100 μM
• 孵育时间：48 小时
• 结果：抑制 CDK1 和 CDK2 的表达。

细胞周期分析

• 细胞系：HCT-116 细胞
• 浓度：0，25，50 或 100 μM
• 孵育时间：24，48 或 72 小时
• 结果：诱导 HCT-116 细胞的周期停滞在 S 和 G2/M 期。

体内研究

Desmethylglycitein（4',6,7-三羟基异黄酮）通过腹腔注射给药（5 或 25 mg/kg；每日一次；持续 20 天），能够抑制小鼠肿瘤的发展，作为有效的抗癌治疗剂，在体外系统中具有潜在的抑瘤或延缓 HCT-116 细胞致瘤性的能力。

动物模型

• 动物：雌性无胸腺裸鼠
• 给药方式：腹腔注射 HCT-116 细胞
• 剂量：5 或 25 mg/kg
• 给药方法：腹腔注射；每日一次，共 20 天
• 结果：减少 HCT-116 异种移植物的生长、体积和重量。

反应信息

• 作为反应物：
  描述：

  4’,6,7-三羟异黄酮 在 palladium on activated charcoal 硫酸 、 氢气 、 溶剂黄146 作用下， 反应 14.0h， 以55%的产率得到6,7,4'-三羟基异黄烷
  参考文献：
  名称：

  Structure–activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2

  摘要：

  Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavanones tend to select against 12-hLO, that isoflavans tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.036
• 作为产物：
  描述：

  对羟基苯乙腈 在 盐酸 、 三氟化硼乙醚 、 水 、 甲基磺酰氯 、 zinc(II) chloride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 4’,6,7-三羟异黄酮
  参考文献：
  名称：

  Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase

  摘要：

  Continuing our search to find more potent and selective 5‐LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5‐LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5‐LOX (IR‐2, HIR‐303, and HIR‐309), with IC50 values at least 10 times lower than those of 12‐LOX, 15‐LOX‐1, and 15‐LOX‐2. Of these three, IR‐2 (6,7‐dihydroxy‐4‐methoxy‐isoflavone, known as texasin) was the most selective 5‐LOX inhibitor, with over 80‐fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7‐dihydroxy versus 7,8‐dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5‐LOX. Two of the most potent/selective inhibitors (HIR‐303 and HIR‐309) were reductive inhibitors and were potent against 5‐LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5‐LOX in vitro and in cellulo.

  DOI：

  10.1111/cbdd.12469

文献信息

• O-methylation of flavonoids by cell-free extracts of calamondin orange
  作者：Gunter Brunet、Ragai K. Ibrahim

  DOI：10.1016/0031-9422(80)85102-8

  日期：——

  hydroxyls of a number of flavonoids, indicating the existence in citrus tissues of ortho, meta, para and 3-O-methyltransferases. The latter, hitherto unreported enzyme, catalysed the formation of 3-O-methyl ethers of galangin and quercetin. The stepwise O-methylation of a number of compounds, especially quercetin and quercetagetin, tends to suggest a coordinated sequence of O-methylations on the surface

  摘要 柑桔（Citrus mitis）的无细胞提取物催化了许多类黄酮的几乎所有羟基的O-甲基化，表明柑橘组织中存在邻位、间位、对位和3-O-甲基转移酶。后者，迄今未报道的酶，催化高良姜素和槲皮素的 3-O-甲基醚的形成。许多化合物的逐步 O-甲基化，尤其是槲皮素和槲皮素，往往表明多酶复合物表面上存在协调的 O-甲基化序列。所使用的类黄酮底物的甲基受体能力与它们的羟基取代模式和它们的负电子密度分布有关。
• METHOD OF IMPROVING STABILITY OF SWEET ENHANCER AND COMPOSITION CONTAINING STABILIZED SWEET ENHANCER
  申请人：TACHDJIAN Catherine

  公开号：US20120041078A1

  公开（公告）日：2012-02-16

  The present invention includes methods of stabilizing one or more sweet enhancers when they are exposed to a light source as well as liquid compositions containing one or more sweet enhancers and one or more photostabilizers.

  本发明包括在甜味增强剂暴露于光源时稳定一个或多个甜味增强剂的方法，以及包含一个或多个甜味增强剂和一个或多个光稳定剂的液体组合物。
• 7-Hydroxy-benzopyran-4-one Derivatives: A Novel Pharmacophore of Peroxisome Proliferator-Activated Receptor α and -γ (PPARα and γ) Dual Agonists
  作者：Azadeh Matin、Navnath Gavande、Moon S. Kim、Nancy X. Yang、Noeris K. Salam、Jane R. Hanrahan、Rebecca H. Roubin、David E. Hibbs

  DOI：10.1021/jm900964r

  日期：2009.11.12

  Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead

  描述了通过结构驱动设计范式发现的新型潜在的双重PPARα和γ双重激动剂的设计，合成和体外生物评价。7-羟基-苯并吡喃-4-酮部分（包括黄酮，黄烷酮和异黄酮）是这些新分子的关键药效​​基团，与贝特类药物和噻唑烷二酮的核心结构相似。从“保健食品”和合成类似物中鉴定出新的PPAR配体。总共筛选了77个分子，包括查耳酮，黄酮，黄烷酮，异黄酮和吡唑衍生物，并进行了双重激动剂的构效关系研究。化合物68，70，72，和76被鉴定为新型有效的PPARα和γ双重激动剂。这些新型分子可能会成为PPAR相关疾病（包括II型糖尿病和代谢综合征）未来的领先者。
• Free-Radical-Scavenging, Antityrosinase, and Cellular Melanogenesis Inhibitory Activities of Synthetic Isoflavones
  作者：Tzy-Ming Lu、Horng-Huey Ko、Lean-Teik Ng、Yen-Pin Hsieh

  DOI：10.1002/cbdv.201400208

  日期：2015.6

  potential of synthetic isoflavones for application in cosmeceuticals. Twenty‐five isoflavones were synthesized and their capacities of free‐radical‐scavenging and mushroom tyrosinase inhibition, as well as their impact on cell viability of B16F10 murine melanoma cells and HaCaT human keratinocytes were evaluated. Isoflavones that showed significant mushroom tyrosinase inhibitory activities were further

  在这项研究中，我们研究了合成异黄酮在药妆品中的应用潜力。合成了 25 种异黄酮，并评估了它们清除自由基和抑制蘑菇酪氨酸酶的能力，以及它们对 B16F10 鼠黑色素瘤细胞和 HaCaT 人角质形成细胞的细胞活力的影响。进一步研究了显示出显着蘑菇酪氨酸酶抑制活性的异黄酮在体外 B16F10 黑素细胞中减少细胞黑色素形成和抗酪氨酸酶活性。在测试的异黄酮中，6-羟基黄豆苷元 (2) 是 ABTS.+ 和 DPPH 的最强清除剂。SC50 值分别为 11.3±0.3 和 9.4±0.1 μM 的自由基。Texasin (20) 表现出最有效的蘑菇酪氨酸酶抑制作用 (IC50 14.9±4.5 μM)，而 retusin (17) 分别显示出对 B16F10 黑素细胞中细胞黑色素形成和抗酪氨酸酶活性的最有效抑制。总之，retusin (17) 和 texasin (20) 都表现出强大的自由基清除能力
• Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities
  作者：Hideyuki Goto、Yoshiyasu Terao、Shuji Akai

  DOI：10.1248/cpb.57.346

  日期：——

  Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10′) were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12—54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E—I) and their biphenyl-ketone derivatives (10E—H) also showed a high activity (ED50=<50 μM), while all of their corresponding isoflavones (8E—I) were not active at all. The 7-hydroxyisoflavanes having either an additional hydroxyl group at the C5-position (9D) or a methoxy group at the C6-position (9J) presented a high activity (ED50=26—32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3′-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10′) by metabolism or biotransformation.

  合成了四十八种异黄酮（8）、三十一种异黄烷（9）以及四十七种联苯酮（10, 10′），这些化合物是由十一种取代酚（11）和六种苯乙酸（12）合成的。其中，有七十五种化合物是新发现的。这些化合物的自由基清除活性在pH 6.0下使用1,1-二苯基-2-吡唑啉酮（DPPH）进行了评估。我们发现，在四十三种含有儿茶酚基的化合物中，三十九种在A环或B环上表现出与儿茶素相似的高活性（ED50=12—54 μM）。在这些情况下，它们结构的其他部分似乎对活性影响不大。许多6-或8-羟基异黄烷（9E—I）及其联苯酮衍生物（10E—H）也显示出高活性（ED50=<50 μM），而它们对应的异黄酮（8E—I）则完全没有活性。具有在C5位增加羟基（9D）或在C6位增加甲氧基（9J）的7-羟基异黄烷则展现出高活性（ED50=26—32 μM）。本研究表明，天然异黄酮通过在C6、C8或C3′位置的羟基化，或通过代谢或生物转化形成异黄烷（9）和/或联苯酮衍生物（10′），具有表现抗氧化活性的可能性。