5,6,7,8-tetrafluoro-2-(2-hydroxy-ethylsulfanyl)-3-methyl-1,4-naphthoquinone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5,6,7,8-tetrafluoro-2-(2-hydroxy-ethylsulfanyl)-3-methyl-1,4-naphthoquinone
• 英文别名: NCS 95397；F-Cpd5；5,6,7,8-Tetrafluoro-2-(2-hydroxyethylsulfanyl)-3-methylnaphthalene-1,4-dione
• 化学式: C₁₃H₈F₄O₃S
• 分子量: 320.264
• InChiKey: WLTTWOPJBJOCSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,5,6,7,8-pentafluoro-3-methl-1,4-naphthoquinone 、 2-巯基乙醇 以 甲醇 为溶剂， 生成 5,6,7,8-tetrafluoro-2-(2-hydroxy-ethylsulfanyl)-3-methyl-1,4-naphthoquinone
  参考文献：
  名称：

  Fluorinated quinoid inhibitor: possible `pure' arylator predicted by the simple theoretical calculation

  摘要：

  We report on the fluorinated form of Cpd 5 as a cell growth inhibitor. This compound is 3-fold more potent than the parent Cpd 5 and is predicted, using the semi-empirical AM1 method to be only an arylator of cysteine-containing proteins, without generating reactive oxygen species. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.009

文献信息

• Fluorinated quinoid inhibitor: possible `pure' arylator predicted by the simple theoretical calculation
  作者：Seung Wook Ham、Jong-In Choe、Mei-Fang Wang、Vincent Peyregne、Brian I Carr

  DOI：10.1016/j.bmcl.2004.05.009

  日期：2004.8

  We report on the fluorinated form of Cpd 5 as a cell growth inhibitor. This compound is 3-fold more potent than the parent Cpd 5 and is predicted, using the semi-empirical AM1 method to be only an arylator of cysteine-containing proteins, without generating reactive oxygen species. (C) 2004 Elsevier Ltd. All rights reserved.
• Fluorinated Cpd 5, a pure arylating K-vitamin derivative, inhibits human hepatoma cell growth by inhibiting Cdc25 and activating MAPK
  作者：Siddhartha Kar、Meifang Wang、Seung Wook Ham、Brian I. Carr

  DOI：10.1016/j.bcp.2006.07.024

  日期：2006.11

  We previously synthesized several K-vitamin derivatives, which are potent growth inhibitors of human tumor cells, including Hep3B human hepatoma cells. Among these, Cpd 5 was the most potent. However, being a quinone derivative, Cpd 5 has the potential for generating toxic reactive oxygen species (ROS). We therefore synthesized a fluorinated derivative of Cpd 5, F-Cpd 5. The calculated reduction potential of F-Cpd 5 was much higher than that for Cpd S and it was not predicted to generate ROS. This was supported by our observation that F-Cpd 5 generated significantly lower ROS than Cpd 5. F-Cpd 5 was three times more potent than Cpd 5 in inhibiting Hep3B cell growth. Interestingly, under identical culture conditions, F-Cpd 5 inhibited mitogen-induced DNA synthesis in normal rat hepatocytes 12-fold less potently than Hep3B cells. F-Cpd 5 was found to induce caspase-3 cleavage and nuclear DNA laddering, evidences for apoptosis. It preferentially inhibited the activities of the cell cycle controlling phosphatases Cdc25A and Cdc25B, by binding to their catalytic cysteines. Consequently, inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2 and Cdk4 were induced. F-Cpd 5 also induced phosphorylation of the MAPK proteins ERK1/2, JNK1/2 and p38 in Hep3B cells and the MAPK inhibitors (U0126, JNKI-II, and SB 203580) antagonized its growth inhibition. F-Cpd 5 inhibited the action of cytosolic ERK phosphatase activity, which likely caused the ERK phosphorylation. F-Cpd 5 thus differentially inhibited growth of normal and tumor cells by preferentially inhibiting the actions of Cdc25A and Cdc25B phosphatases and inducing MAPK phosphorylation. (c) 2006 Elsevier Inc. All rights reserved.