(E)-[1-(3-indolyl)-2-(4-N-methylpyridiniumyl)] ethylene iodide salt

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-[1-(3-indolyl)-2-(4-N-methylpyridiniumyl)] ethylene iodide salt
• 英文别名: (E)-4-[2-(1H-indol-3-yl)-vinyl]-1-methyl-pyridinium iodide；(E)-4-(2-(1H-indol-3-yl)vinyl)-N-methylpyridinium iodide；(E)-4-(2-[1H-indol-3-yl]vinyl)-N-methylpyridinium iodide；(E)-4-(1H-indol-3-ylvinyl)-N-methylpyridinium iodide；4-[(E)-2-(indol-3-yl)ethenyl]-N-methylpyridinium iodide；3-[2-(1-methylpyridin-1-ium-4-yl)ethenyl]-1H-indole;iodide
• 化学式: C₁₆H₁₅N₂*I
• 分子量: 362.213
• InChiKey: UURAKYSOOXPORG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  15.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-[1-(3-indolyl)-2-(4-N-methylpyridiniumyl)] ethylene iodide salt 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 0.03h， 以93%的产率得到3-[2-(1-methyl-1H-pyridin-4-ylidene)-ethylidene]-3H-indole
  参考文献：
  名称：

  Vinylogous anhydro bases of pyridylindoles

  摘要：

  DOI：

  10.1007/bf00496604
• 作为产物：
  描述：

  芦竹碱 在 三丁基膦 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 (E)-[1-(3-indolyl)-2-(4-N-methylpyridiniumyl)] ethylene iodide salt
  参考文献：
  名称：

  结合了5-氟尿嘧啶和靶向线粒体的亲脂性阳离子：设计，合成和生物学评估† •

  摘要：

  5-氟尿嘧啶（5-FU）通过易碎键与F16相连，以选择性地靶向癌症线粒体，从而产生共轭化合物，包括F16–5-FU，F16–OOC-FU，F16–NHOC-FU和F16–SS-FU 。F16–OOC-FU降低了5-FU对非肿瘤细胞系的抗增殖活性，与二硫苏糖醇（DTT）一起使用时，F16–SS-FU的细胞毒性显着增加。

  DOI：

  10.1039/c6md00268d

文献信息

• Conjugated 5-fluorouracil with mitochondria-targeting lipophilic cation: design, synthesis and biological evaluation
  作者：Jia Wang、Xiao-Yang Fan、Li-Yun Yang、Huan He、Rong Huang、Feng-Lei Jiang、Yi Liu

  DOI：10.1039/c6md00268d

  日期：——

  5-Fluorouracil (5-FU) was linked with F16 by vulnerable bonds to selectively target cancer mitochondria which resulted in conjugated compounds, including F16–5-FU, F16–OOC-FU, F16–NHOC-FU and F16–SS-FU. F16–OOC-FU decreased the antiproliferative activity of 5-FU on the nontumor cell line, and the cytotoxicity of F16–SS-FU significantly increased when administered with dithiothreitol (DTT).

  5-氟尿嘧啶（5-FU）通过易碎键与F16相连，以选择性地靶向癌症线粒体，从而产生共轭化合物，包括F16–5-FU，F16–OOC-FU，F16–NHOC-FU和F16–SS-FU 。F16–OOC-FU降低了5-FU对非肿瘤细胞系的抗增殖活性，与二硫苏糖醇（DTT）一起使用时，F16–SS-FU的细胞毒性显着增加。
• Synthesis of F16 conjugated with 5-fluorouracil and biophysical investigation of its interaction with bovine serum albumin by a spectroscopic and molecular modeling approach
  作者：Chen Xiang、Dong-Wei Li、Zu-De Qi、Feng-Lei Jiang、Yu-Shu Ge、Yi Liu

  DOI：10.1002/bio.2447

  日期：2013.11

  5-Fluorouracil (5-FU) has been widely used as a chemotherapy agent in the treatment of many types of solid tumors. Investigation of its antimetabolites led to the development of an entire class of fluorinated pyrimidines. However, the toxicity profile associated with 5-FU is significant and includes diarrhea, mucositis, hand–foot syndrome and myelosuppression. In aiming at reducing of the side effects of 5-FU, we have designed and synthesized delocalized lipophilic cations (DLCs) as a vehicle for the delivery of 5-FU. DLCs accumulate selectively in the mitochondria of cancer cells because of the high mitochondrial transmembrane potential (ΔΨm). Many DLCs exhibited anti-cancer efficacy and were explored as potential anti-cancer drugs based on their selective accumulation in the mitochondria of cancer cells. F16, the DLC we used as a vehicle, is a small molecule that selectively inhibits tumor cell growth and dissipates mitochondrial membrane potential. The binding of the conjugate F16–5-FU to bovine serum albumin (BSA) was investigated using spectroscopic and molecular modeling approaches. Fluorescence quenching constants were determined using the Stern–Volmer equation to provide a measure of the binding affinity between F16–5-FU and BSA. The activation energy of the interaction between F16–5-FU and BSA was calculated and the unusually high value was discussed in terms of the special structural block indicated by the molecular modeling approach. Molecular modeling showed that F16–5-FU binds to human serum albumin in site II, which is consistent with the results of site-competitive replacement experiments. It is suggested that hydrophobic and polar forces played important roles in the binding reaction, in accordance with the results of thermodynamic experiments. Copyright © 2012 John Wiley & Sons, Ltd.

  5-氟尿嘧啶（5-FU）已被广泛用作治疗多种实体瘤的化疗药物。通过对其抗代谢物的研究，开发出了一整类氟化嘧啶。然而，5-FU 的毒性很大，包括腹泻、粘膜炎、手足综合征和骨髓抑制。为了减少 5-FU 的副作用，我们设计并合成了脱定位亲脂阳离子（DLCs），作为 5-FU 的载体。由于线粒体跨膜电位（ΔΨm）较高，DLCs 可选择性地聚集在癌细胞的线粒体中。许多 DLC 具有抗癌功效，并根据其在癌细胞线粒体中的选择性积累被探索为潜在的抗癌药物。我们用作载体的 DLC F16 是一种选择性抑制肿瘤细胞生长并降低线粒体膜电位的小分子。我们利用光谱和分子建模方法研究了 F16-5-FU 与牛血清白蛋白（BSA）的结合。利用斯特恩-沃尔默方程测定了荧光淬灭常数，以衡量 F16-5-FU 与 BSA 之间的结合亲和力。计算了 F16-5-FU 和 BSA 之间相互作用的活化能，并根据分子建模方法所显示的特殊结构块讨论了异常高的活化能值。分子建模显示，F16-5-FU 与人血清白蛋白结合的位点是位点 II，这与位点竞争性置换实验的结果一致。热力学实验结果表明，疏水作用力和极性作用力在结合反应中发挥了重要作用。Copyright © 2012 John Wiley & Sons, Ltd. All Rights Reserved.
• MITOCHONDRIA-TARGETED THERANOSTIC AGENTS
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20150336993A1

  公开（公告）日：2015-11-26

  Mitochondria-targeted theranostic agents and methods of using them diagnostically and therapeutically are disclosed. In particular, the invention relates to theranostic agents comprising F16, or analogues thereof, conjugated to alkyltriphenylphosphonium lipophilic cations, and their uses in medical imaging and treatment of diseases associated with mitochondrial dysfunction, including cancer.

  本发明涉及定向线粒体治疗剂和使用它们进行诊断和治疗的方法。特别是，本发明涉及包含F16或其类似物与烷基三苯基膦脂溶性阳离子偶联的治疗剂，以及它们在医学成像和治疗与线粒体功能障碍有关的疾病，包括癌症方面的应用。
• Combinatorial Approach to Organelle-Targeted Fluorescent Library Based on the Styryl Scaffold
  作者：Gustavo R. Rosania、Jae Wook Lee、Liang Ding、Hai-Shin Yoon、Young-Tae Chang

  DOI：10.1021/ja027587x

  日期：2003.2.1

  The first fluorescent styryl dye library with a broad color range was synthesized by combinatorial condensation of various aldehydes and methyl pyridinium compounds, and their applications as organelle specific staining probes were demonstrated.
• Synthesis, spectral properties of cell-permeant dimethine cyanine dyes and their application as fluorescent probes in living cell imaging and flow cytometry
  作者：X.H. Zhang、Q. Liu、H.J. Shi、L.Y. Wang、Y.L. Fu、X.C. Wei、L.F. Yang

  DOI：10.1016/j.dyepig.2013.09.011

  日期：2014.1

  A series of dimethine cyanine dyes, used as fluorescent probes, were synthesized under microwave irradiation, and identified by H-1 NMR, IR, elemental analysis and HRMS. The investigation of their spectral properties in phosphate-buffer saline (PBS) showed that the absorption and emission maxima of the dyes were in the region 370-480 nm and 471-569 nm, respectively. The properties of the dyes as fluorescent probes for living cells imaging and flow cytometry were investigated. The results showed that dyes 1, 2, 8 or 9 could penetrate an intact cell membrane, stained the cell nuclear and exhibited bright fluorescence. Little background interference, low cell cytotoxicity and little photobleaching were showed during the imaging tests. The dyes 1, 8 and 9 could be applied in flow cytometry and dye 1/PI, dye 8/PI or dye 9/PI couple could be proposed as double staining agents to measure sperm cell viability. Thus the dyes represented the cell-permeant fluorescent probes. (C) 2013 Elsevier Ltd. All rights reserved.