2,6-bis(bis(5-methoxy-1H-indol-3-yl)methyl)pyridine

• 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: 2,6-bis(bis(5-methoxy-1H-indol-3-yl)methyl)pyridine
• 英文别名: 3-[[6-[bis(5-methoxy-1H-indol-3-yl)methyl]pyridin-2-yl]-(5-methoxy-1H-indol-3-yl)methyl]-5-methoxy-1H-indole
• 化学式: C₄₃H₃₇N₅O₄
• 分子量: 687.798
• InChiKey: VFNFRHSGHFFVQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吡啶-2,6-二甲醛 、 5-甲氧基吲哚 在 ammonium cerium (IV) nitrate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以45%的产率得到2,6-bis(bis(5-methoxy-1H-indol-3-yl)methyl)pyridine
  参考文献：
  名称：

  Anticancer efficacy of unique pyridine-based tetraindoles

  摘要：

  Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G(2)/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.032

文献信息

• Anticancer efficacy of unique pyridine-based tetraindoles
  作者：Chih-Wei Fu、Yun-Jung Hsieh、Tzu Ting Chang、Chia-Ling Chen、Cheng-Yu Yang、Anne Liao、Pei-Wen Hsiao、Wen-Shan Li

  DOI：10.1016/j.ejmech.2015.09.032

  日期：2015.11

  Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G(2)/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy. (C) 2015 Elsevier Masson SAS. All rights reserved.