COBRA-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: COBRA-1
• 英文别名: (1R)-1-[(2R,5R)-5-[(1S)-1-hydroxypent-4-enyl]oxolan-2-yl]tridecan-1-ol
• 化学式: C₂₂H₄₂O₃
• 分子量: 354.574
• InChiKey: XJYQGNNBDGDYCE-DXBBTUNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  25
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-1-((2R,5R)-(S)-5-Oxiranyl-tetrahydro-furan-2-yl)-tridecan-1-ol 、 烯丙基溴化镁 在 copper(l) iodide 作用下， 以 四氢呋喃 为溶剂， 生成 COBRA-1
  参考文献：
  名称：

  Synthesis and Biological Evaluation As Microtubule-Active Agents of Several Tetrahydrofuran and Spiroacetal Derivatives

  摘要：

  本文介绍了几种含有四氢呋喃和螺缩醛结构片段的分子的立体选择性制备方法。研究了它们的细胞毒性程度及其与微管蛋白的相互作用。研究证实，四氢呋喃衍生物具有细胞毒性，但与以前的报告不同的是，研究发现这种细胞毒性并不是由于与微管网络的相互作用造成的。此外，与以前关于密切相关化合物的报告不同的是，螺缩醛衍生物确实与微管蛋白发生了相互作用，尽管其确切机制和结合位点仍有待确定。

  DOI：

  10.2174/0929867311320090006

文献信息

• COBRA-1, A rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent
  作者：Shyi-Tai Jan、Chen Mao、Alexei O Vassilev、Christopher S Navara、Fatih M Uckun

  DOI：10.1016/s0960-894x(00)00212-2

  日期：2000.6

  A novel mono-THF containing synthetic anticancer drug, COBRA-1, was designed for targeting a previously unrecognized unique narrow binding cavity on the surface of alpha-tubulin. COBRA-1 inhibited GTP-induced tubulin polymerization in cell-free tubulin turbidity assays. Treatment of human breast cancer and brain tumor (glioblastoma) cells with COBRA-1 caused destruction of microtubule organization and apoptosis. Like other microtubule-interfering agents, COBRA-1 activated the pro-apoptotic c-Jun N-terminal kinase (JNK) signal transduction pathway, as evidenced by rapid induction of c-jun expression. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and Biological Evaluation As Microtubule-Active Agents of Several Tetrahydrofuran and Spiroacetal Derivatives
  作者：M. Carda、J. Murga、J. Panos、C. A. Angulo-Pachon、J. Garcia-Pla、S. Diaz-Oltra、J. A. Marco、C. Trigili、M. Redondo-Horcajo、J. F. Diaz、I. Barasoain

  DOI：10.2174/0929867311320090006

  日期：2013.2.1

  The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described. Their degree of cytotoxicity and their interactions with tubulin have been investigated. It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network. Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established.

  本文介绍了几种含有四氢呋喃和螺缩醛结构片段的分子的立体选择性制备方法。研究了它们的细胞毒性程度及其与微管蛋白的相互作用。研究证实，四氢呋喃衍生物具有细胞毒性，但与以前的报告不同的是，研究发现这种细胞毒性并不是由于与微管网络的相互作用造成的。此外，与以前关于密切相关化合物的报告不同的是，螺缩醛衍生物确实与微管蛋白发生了相互作用，尽管其确切机制和结合位点仍有待确定。