7-hydroxy-4-dimethoxymethyl-1,6-dimethylquinolin-2(1H)-one | 828277-19-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-hydroxy-4-dimethoxymethyl-1,6-dimethylquinolin-2(1H)-one
• 英文别名: 4-(dimethoxymethyl)-7-hydroxy-1,6-dimethylquinolin-2-one
• CAS: 828277-19-6
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: SJGQPVQAYVAKFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4-dimethoxymethyl-1,6-dimethylquinolin-2(1H)-one 在 potassium carbonate 、 cesium fluoride 作用下， 以 丙酮 为溶剂， 反应 10.0h， 生成 4-dimethoxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one
  参考文献：
  名称：

  4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one Induces Mitochondrial Dysfunction and Apoptosis upon Its Intracellular Oxidation

  摘要：

  We investigated the mechanism of cell death induced by a furoquinolinone derivative, namely, 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ), in the dark. Mitochondrial depolarization was found to be a causative event in HOFQ-induced apoptosis that was blunted either by replacing the 4-hydroxymethyl group with a methyl one, or by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH). In vitro enzymatic assay demonstrated that HOFQ is a substrate of ADH. In isolated mitochondria HOFQ was without effect, whereas in the presence of ADH and NAD+ it caused the opening of the permeability transition pore, indicating that HOFQ-oxidized products affect mitochondrial function directly. Finally, an analogue bearing the formyl group at the C-4 position mimicked all the effects exerted by HOFQ In conclusion, these results suggest that the direct action on mitochondria of HOFQ-oxidized products are responsible for their cytotoxicity, which might be exacerbated, but hardly determined, by photodynamic action and/or binding to DNA.

  DOI：

  10.1021/jm0493919
• 作为产物：
  描述：

  7-acetoxy-1,6-dimethyl-2-oxoquinoline-4-carboxaldehyde 、 原甲酸三甲酯 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以63%的产率得到7-hydroxy-4-dimethoxymethyl-1,6-dimethylquinolin-2(1H)-one
  参考文献：
  名称：

  4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one Induces Mitochondrial Dysfunction and Apoptosis upon Its Intracellular Oxidation

  摘要：

  We investigated the mechanism of cell death induced by a furoquinolinone derivative, namely, 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ), in the dark. Mitochondrial depolarization was found to be a causative event in HOFQ-induced apoptosis that was blunted either by replacing the 4-hydroxymethyl group with a methyl one, or by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH). In vitro enzymatic assay demonstrated that HOFQ is a substrate of ADH. In isolated mitochondria HOFQ was without effect, whereas in the presence of ADH and NAD+ it caused the opening of the permeability transition pore, indicating that HOFQ-oxidized products affect mitochondrial function directly. Finally, an analogue bearing the formyl group at the C-4 position mimicked all the effects exerted by HOFQ In conclusion, these results suggest that the direct action on mitochondria of HOFQ-oxidized products are responsible for their cytotoxicity, which might be exacerbated, but hardly determined, by photodynamic action and/or binding to DNA.

  DOI：

  10.1021/jm0493919

文献信息

• 4-Hydroxymethyl-1,6,8-trimethylfuro[2,3-<i>h</i>]quinolin-2(1<i>H</i>)-one Induces Mitochondrial Dysfunction and Apoptosis upon Its Intracellular Oxidation
  作者：Adriana Chilin、Giuliano Dodoni、Christian Frezza、Adriano Guiotto、Vera Barbieri、Fabio Di Lisa、Marcella Canton

  DOI：10.1021/jm0493919

  日期：2005.1.1

  We investigated the mechanism of cell death induced by a furoquinolinone derivative, namely, 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ), in the dark. Mitochondrial depolarization was found to be a causative event in HOFQ-induced apoptosis that was blunted either by replacing the 4-hydroxymethyl group with a methyl one, or by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH). In vitro enzymatic assay demonstrated that HOFQ is a substrate of ADH. In isolated mitochondria HOFQ was without effect, whereas in the presence of ADH and NAD+ it caused the opening of the permeability transition pore, indicating that HOFQ-oxidized products affect mitochondrial function directly. Finally, an analogue bearing the formyl group at the C-4 position mimicked all the effects exerted by HOFQ In conclusion, these results suggest that the direct action on mitochondria of HOFQ-oxidized products are responsible for their cytotoxicity, which might be exacerbated, but hardly determined, by photodynamic action and/or binding to DNA.