2-(4-dodecyloxyphenylazo)pyridine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-dodecyloxyphenylazo)pyridine
• 英文别名: (4-Dodecoxyphenyl)-pyridin-2-yldiazene；(4-dodecoxyphenyl)-pyridin-2-yldiazene
• 化学式: C₂₃H₃₃N₃O
• 分子量: 367.535
• InChiKey: XDPXNGQIWSONNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [RuCl2(benzene)]2 、 ammonium hexafluorophosphate 、 2-(4-dodecyloxyphenylazo)pyridine 以 甲醇 为溶剂， 反应 28.0h， 以79%的产率得到
  参考文献：
  名称：

  Cytotoxicity of η-areneruthenium-based molecules to glioblastoma cells and their recognition by multidrug ABC transporters

  摘要：

  A new series of amphiphilic eta(6)-areneruthenium(II) compounds containing phenylazo ligands (group I: compounds la, 1b, 2a and 2b) and phenyloxadiazole ligands (group II: compounds 3a, 3b, 4a and 4b) were synthesized and characterized for their anti-glioblastoma activity. The effects of the amphiphilic eta(6)-areneruthenium(II) complexes on the viability of three human glioblastoma cell lines, U251, U87MG and T98G, were evaluated. The azo-derivative ruthenium complexes (group I) showed high cytotoxicity to all cell lines, whilst most oxadiazole-derivative complexes (group II) were less cytotoxic, except for compound 4a. The cationic complexes 2a, 2b and 4b were more cytotoxic than the neutral complexes. Compounds 2a and 2b caused a significant reduction in the percentage of cells in the G0/G1 phase, with concomitant increases in the G2/M phase and fragmented DNA in the T98G cell line. The eta(6)-areneruthenium(11) compounds were also tested in cell lines that overexpress the multidrug ABC transporters P-gp, MRP1 and ABCG2. Compounds 2b and 4a were substrates for the P-gp protein, with resistance indexes of 8.6 and 1.9, respectively. Compound 2b was also a substrate for ABCG2 and MRP1 proteins, with lower resistance indexes (1.8 and 1.6, respectively). The contribution of multidrug ABC transporters to the cytotoxicity of compound 2b in T98G cells was evidenced, since verapamil (a characteristic inhibitor of MRP1) increased the cytotoxicity of compound 2b at concentrations up to 20 mu mol L-1, whilst GP120918 and Ko143 (specific inhibitors of P-gp and ABCG2, respectively) had no significant effect. In addition, we showed that compound 2b interacts with glutathione (GSH), which could explain its cellular efflux by MRP1. Our results showed that the amphiphilic eta(6)-areneruthenium(II) complexes are promising anti-glioblastoma compounds, especially compound 2b, which was cytotoxic for all three cell lines, although it is transported by the three main multidrug ABC transporters. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.026
• 作为产物：
  描述：

  2-肼吡啶 在 硫酸 、 potassium carbonate 作用下， 以 水 、 丁酮 为溶剂， 反应 25.5h， 生成 2-(4-dodecyloxyphenylazo)pyridine
  参考文献：
  名称：

  Cytotoxicity of η-areneruthenium-based molecules to glioblastoma cells and their recognition by multidrug ABC transporters

  摘要：

  A new series of amphiphilic eta(6)-areneruthenium(II) compounds containing phenylazo ligands (group I: compounds la, 1b, 2a and 2b) and phenyloxadiazole ligands (group II: compounds 3a, 3b, 4a and 4b) were synthesized and characterized for their anti-glioblastoma activity. The effects of the amphiphilic eta(6)-areneruthenium(II) complexes on the viability of three human glioblastoma cell lines, U251, U87MG and T98G, were evaluated. The azo-derivative ruthenium complexes (group I) showed high cytotoxicity to all cell lines, whilst most oxadiazole-derivative complexes (group II) were less cytotoxic, except for compound 4a. The cationic complexes 2a, 2b and 4b were more cytotoxic than the neutral complexes. Compounds 2a and 2b caused a significant reduction in the percentage of cells in the G0/G1 phase, with concomitant increases in the G2/M phase and fragmented DNA in the T98G cell line. The eta(6)-areneruthenium(11) compounds were also tested in cell lines that overexpress the multidrug ABC transporters P-gp, MRP1 and ABCG2. Compounds 2b and 4a were substrates for the P-gp protein, with resistance indexes of 8.6 and 1.9, respectively. Compound 2b was also a substrate for ABCG2 and MRP1 proteins, with lower resistance indexes (1.8 and 1.6, respectively). The contribution of multidrug ABC transporters to the cytotoxicity of compound 2b in T98G cells was evidenced, since verapamil (a characteristic inhibitor of MRP1) increased the cytotoxicity of compound 2b at concentrations up to 20 mu mol L-1, whilst GP120918 and Ko143 (specific inhibitors of P-gp and ABCG2, respectively) had no significant effect. In addition, we showed that compound 2b interacts with glutathione (GSH), which could explain its cellular efflux by MRP1. Our results showed that the amphiphilic eta(6)-areneruthenium(II) complexes are promising anti-glioblastoma compounds, especially compound 2b, which was cytotoxic for all three cell lines, although it is transported by the three main multidrug ABC transporters. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.026

文献信息

• Cytotoxicity of η-areneruthenium-based molecules to glioblastoma cells and their recognition by multidrug ABC transporters
  作者：Jaqueline Pazinato、Otávio M. Cruz、Karine P. Naidek、Amanda R.A. Pires、Eduard Westphal、Hugo Gallardo、Hélène Baubichon-Cortay、Maria E.M. Rocha、Glaucia R. Martinez、Sheila M.B. Winnischofer、Attilio Di Pietro、Herbert Winnischofer

  DOI：10.1016/j.ejmech.2018.02.026

  日期：2018.3

  A new series of amphiphilic eta(6)-areneruthenium(II) compounds containing phenylazo ligands (group I: compounds la, 1b, 2a and 2b) and phenyloxadiazole ligands (group II: compounds 3a, 3b, 4a and 4b) were synthesized and characterized for their anti-glioblastoma activity. The effects of the amphiphilic eta(6)-areneruthenium(II) complexes on the viability of three human glioblastoma cell lines, U251, U87MG and T98G, were evaluated. The azo-derivative ruthenium complexes (group I) showed high cytotoxicity to all cell lines, whilst most oxadiazole-derivative complexes (group II) were less cytotoxic, except for compound 4a. The cationic complexes 2a, 2b and 4b were more cytotoxic than the neutral complexes. Compounds 2a and 2b caused a significant reduction in the percentage of cells in the G0/G1 phase, with concomitant increases in the G2/M phase and fragmented DNA in the T98G cell line. The eta(6)-areneruthenium(11) compounds were also tested in cell lines that overexpress the multidrug ABC transporters P-gp, MRP1 and ABCG2. Compounds 2b and 4a were substrates for the P-gp protein, with resistance indexes of 8.6 and 1.9, respectively. Compound 2b was also a substrate for ABCG2 and MRP1 proteins, with lower resistance indexes (1.8 and 1.6, respectively). The contribution of multidrug ABC transporters to the cytotoxicity of compound 2b in T98G cells was evidenced, since verapamil (a characteristic inhibitor of MRP1) increased the cytotoxicity of compound 2b at concentrations up to 20 mu mol L-1, whilst GP120918 and Ko143 (specific inhibitors of P-gp and ABCG2, respectively) had no significant effect. In addition, we showed that compound 2b interacts with glutathione (GSH), which could explain its cellular efflux by MRP1. Our results showed that the amphiphilic eta(6)-areneruthenium(II) complexes are promising anti-glioblastoma compounds, especially compound 2b, which was cytotoxic for all three cell lines, although it is transported by the three main multidrug ABC transporters. (C) 2018 Elsevier Masson SAS. All rights reserved.