Q39 | 936829-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: Q39
• 英文别名: 3-(4-bromophenyl)-2-(ethylsulfonyl)-6-methylquinoxaline 1,4-dioxide；2-(4-bromophenyl)-3-ethylsulfonyl-7-methyl-4-oxidoquinoxalin-1-ium 1-oxide
• CAS: 936829-95-7
• 化学式: C₁₇H₁₅BrN₂O₄S
• 分子量: 423.287
• InChiKey: MHYCOGDEWYAFLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  88.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 间氯过氧苯甲酸 作用下， 生成 Q39
  参考文献：
  名称：

  Q39, a novel synthetic Quinoxaline 1,4-Di-N-oxide compound with anti-cancer activity in hypoxia

  摘要：

  Hypoxia is one of the inevitable circumstances in various tumors and results in tumor resistance to radiotherapy and chemotherapy. The present data showed that 3-(4-bromophenyl)-2-(ethylsulfonyl)-6-methylquinoxaline 1,4-dioxide (Q39), derived from Quinoxaline 1,4-Di-N-oxide, possessed high anti-cancer activity in hypoxia. Cytotoxicity assay demonstrated that Q39 is a potential and high efficient anti-cancer compound in all tested cell lines with IC50 values of 0.18 +/- 0.03-8.88 +/- 1.12 mu M in hypoxia and 0.33 +/- 0.04-8.74 +/- 1.28 mu M in normoxia. In the following work concerning the mechanism of Q39 in hypoxia, we confirmed that Q39 could cause the apoptosis of K562 cells in a time-dependent manner. By fluorescence stain assay, Q39-induced mitochondria membrane potential (Delta Psi(m)) loss was observed in K562 cells in hypoxia. Based on the western blotting, Q39 decreased the protein expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in hypoxia. The compound caused the activation of caspase-3 and subsequent cleavage of its substrate poly (ADP-ribose) polymerase (PARP) in hypoxia. Meanwhile, we found the upregulation of Bax by Q39 in K562 cells as well as the downregulation of Bcl-2. Q39 also influenced the expression of Mitogen-Activated Protein Kinase (MAPKs) and other proteins relative to mitochondria induced apoptosis. In addition, Q39-mediated apoptosis was not reversed after treatment with the JNK-specific inhibitor. In summary, the present study demonstrated Q39 was a novel compound against cancer cells in hypoxia. The mitochondrial pathway mediated by Bcl-2 protein family and MAPKs and the HIF-1 pathway might be involved in signaling Q39-induced apoptosis. (C) 2007 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2007.12.006