5,3'-dihydroxy-6,7-dimethoxyflavone

• 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: 5,3'-dihydroxy-6,7-dimethoxyflavone
• 英文别名: 5-Hydroxy-2-(3-hydroxyphenyl)-6,7-dimethoxychromen-4-one
• 化学式: C₁₇H₁₄O₆
• 分子量: 314.295
• InChiKey: HGMXYCLTWNAEBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,3'-dihydroxy-6,7-dimethoxyflavone 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 生成 5-Hydroxy-6,7-dimethoxy-2-[3-[4-[(2-methoxyphenyl)methyl-methylamino]butoxy]phenyl]chromen-4-one
  参考文献：
  名称：

  Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional agents for the treatment of Alzheimer's disease

  摘要：

  A series of scutellarein-O-alkylamine derivatives were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 16d demonstrated significant metal chelating properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative activity, and excellent inhibitory effects on self-induced A beta(1-42) aggregation, Cu2+-induced A beta(1-42) aggregation, human AChE-induced A beta(1-40) aggregation and disassembled Cu2+-induced aggregation of the well-structured A beta(1-42) fibrils. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that 16d binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Moreover, compound 16d showed a good protective effect against H2O2-induced PC12 cell injury, with low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Thus, 16d was shown to be an interesting multifunctional lead compound worthy of further study. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.063
• 作为产物：
  描述：

  2,3,4-三甲氧基-6-羟基苯乙酮 在 aluminum (III) chloride 、 硫酸 、 potassium iodide 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 73.67h， 生成 5,3'-dihydroxy-6,7-dimethoxyflavone
  参考文献：
  名称：

  Multifunctional scutellarin–rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer’s disease

  摘要：

  To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6 mu M, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.005

文献信息

• Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional agents for the treatment of Alzheimer's disease
  作者：Zhipei Sang、Xiaoming Qiang、Yan Li、Wen Yuan、Qiang Liu、Yikun Shi、Wei Ang、Youfu Luo、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.ejmech.2015.02.063

  日期：2015.4

  A series of scutellarein-O-alkylamine derivatives were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 16d demonstrated significant metal chelating properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative activity, and excellent inhibitory effects on self-induced A beta(1-42) aggregation, Cu2+-induced A beta(1-42) aggregation, human AChE-induced A beta(1-40) aggregation and disassembled Cu2+-induced aggregation of the well-structured A beta(1-42) fibrils. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that 16d binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Moreover, compound 16d showed a good protective effect against H2O2-induced PC12 cell injury, with low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Thus, 16d was shown to be an interesting multifunctional lead compound worthy of further study. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Multifunctional scutellarin–rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer’s disease
  作者：Zhipei Sang、Yan Li、Xiaoming Qiang、Ganyuan Xiao、Qiang Liu、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.bmc.2015.01.005

  日期：2015.2

  To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6 mu M, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD. (c) 2015 Elsevier Ltd. All rights reserved.