7-hydroxy-4-methoxymethyl-6-methylquinolin-2(1H)-one | 406169-90-2

• 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-methoxymethyl-6-methylquinolin-2(1H)-one
• 英文别名: 7-hydroxy-4-methoxymethyl-6-methylquinolin-2-one；2(1H)-Quinolinone, 7-hydroxy-4-(methoxymethyl)-6-methyl-；7-hydroxy-4-(methoxymethyl)-6-methyl-1H-quinolin-2-one
• CAS: 406169-90-2
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: JCKZAYWKDMRASP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4-methoxymethyl-6-methylquinolin-2(1H)-one 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 72.0h， 生成 4-methoxymethyl-1,6-dimethyl-7-propargyloxyquinolin-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：

  2,4-二氨基甲苯 在 硫酸 、 水 、 sodium nitrite 作用下， 反应 24.0h， 生成 7-hydroxy-4-methoxymethyl-6-methylquinolin-2(1H)-one
  参考文献：
  名称：

  新型呋喃[2,3-h]喹啉-2（1H）-one的合成及生物学评价。

  摘要：

  合成了一种新的呋喃喹啉酮衍生物，即4-羟甲基-1,6,8-三甲基呋喃[2,3-h]喹啉-2（1H）-one（HOFQ），并对其生物学活性进行了研究。通过UVA激活，HOFQ在Ehrlich腹水细胞中诱导了强大的抗增殖作用，使其失去了通过移植传播肿瘤的能力。HOFQ表现出较差的遗传毒性和皮肤光毒性。实际上，HOFQ敏化形成DNA-蛋白质交联，但不形成链间交联。因此，HOFQ似乎是用于PUVA光化学疗法和光采的新药。

  DOI：

  10.1021/jm010993r

文献信息

• Synthesis and Biological Evaluation of a New Furo[2,3-<i>h</i>]quinolin-2(1<i>H</i>)-one
  作者：Adriana Chilin、Christine Marzano、Adriano Guiotto、Francarosa Baccichetti、Francesco Carlassare、Franco Bordin

  DOI：10.1021/jm010993r

  日期：2002.2.1

  A new furoquinolinone derivative, namely 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ), was synthesized and its biological activity studied. By UVA activation, HOFQ induced strong antiproliferative effects in Ehrlich ascite cells, which lost their ability to transmit the tumor by transplantation. HOFQ exhibited poor genotoxicity and absence of skin phototoxicity. Actually, HOFQ

  合成了一种新的呋喃喹啉酮衍生物，即4-羟甲基-1,6,8-三甲基呋喃[2,3-h]喹啉-2（1H）-one（HOFQ），并对其生物学活性进行了研究。通过UVA激活，HOFQ在Ehrlich腹水细胞中诱导了强大的抗增殖作用，使其失去了通过移植传播肿瘤的能力。HOFQ表现出较差的遗传毒性和皮肤光毒性。实际上，HOFQ敏化形成DNA-蛋白质交联，但不形成链间交联。因此，HOFQ似乎是用于PUVA光化学疗法和光采的新药。
• 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.