3,7-bis((2-(4-bromophenyl)ethyl)(methyl)amino)phenothiazin-5-ium iodide | 1361990-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3,7-bis((2-(4-bromophenyl)ethyl)(methyl)amino)phenothiazin-5-ium iodide
• 英文别名: 2-(4-Bromophenyl)ethyl-[7-[2-(4-bromophenyl)ethyl-methylamino]phenothiazin-3-ylidene]-methylazanium;iodide
• CAS: 1361990-87-5
• 化学式: C₃₀H₂₈Br₂N₃S*I
• 分子量: 749.351
• InChiKey: XJCSWBSENYMOBB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  5.62
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  19.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  吩噻嗪 在 碘 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 3,7-bis((2-(4-bromophenyl)ethyl)(methyl)amino)phenothiazin-5-ium iodide
  参考文献：
  名称：

  Structure-based optimization of FDA-approved drug methylene blue as a c-myc G-quadruplex DNA stabilizer

  摘要：

  G-quadruplexes are non-canonical DNA secondary structures putatively present in the promoter regions of oncogenes in the human genome. The targeting of promoter G-quadruplex structures to repress oncogene transcription represents a potential anticancer strategy. Here, we have used high-throughput virtual screening to identify FDA-approved drug methylene blue (MB) as a promising scaffold for binding the c-myc oncogene G-quadruplex DNA. Based on molecular docking analysis of MB to the c-myc G-quadruplex, we designed and screened 50 MB derivatives containing side chains that could interact with the G-quadruplex grooves. As a proof-of-concept, the highest-scoring compounds were synthesized and the interactions with the c-myc G-quadruplex were investigated using the FID assay. The results showed that the methylene blue derivatives 6a-c were able to bind to the c-myc G-quadruplex with greater binding affinity compared to the known G-quadruplex binding ligand, crystal violet. The activity of the most potent compound identified from the FID assay, 6b, as an inhibitor for polymerase-drive DNA extension was examined using a PCR-stop assay and compared against that of the parent compound methylene blue. The results of the PCR-stop assay showed that the addition of the side chain improved the activity of the derivatives as an inhibitor compared to the parent compound. The MB derivative 6b was shown to be highly selective towards c-myc G-quadruplex over double-stranded DNA and other cellular biological models, and displayed higher cytoxicity against human hepatocarcinoma cells compared to the parent compound, MB. biologically relevant G-quadruplexes using UV-visible spectroscopy and mass spectrometry, respectively. The MB derivative 6b could induce or stabilize c-myc G-quadruplex formation in both cell-free and (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biochi.2011.02.013