5-(2-(3,4,5-trimethoxyphenyl)-1H-benzo[d]imidazol-5-yl)benzo[c][1,2,5]selenadiazole | 1620912-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-(2-(3,4,5-trimethoxyphenyl)-1H-benzo[d]imidazol-5-yl)benzo[c][1,2,5]selenadiazole
• 英文别名: 5-[2-(3,4,5-trimethoxyphenyl)-3H-benzimidazol-5-yl]-2,1,3-benzoselenadiazole
• CAS: 1620912-49-3
• 化学式: C₂₂H₁₈N₄O₃Se
• 分子量: 465.37
• InChiKey: CCMCPTLXICBLNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(benzo[c][1,2,5]selenadiazol-5-yl)benzene-1,2-diamine 、 3,4,5-三甲氧基苯甲醛 在 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以22%的产率得到5-(1-(3,4,5-trimethoxybenzyl)-2-(3,4,5-trimethoxyphenyl)-1H-benzo[d]imidazol-5-yl)benzo[c][1,2,5]selenadiazole
  参考文献：
  名称：

  Selenadiazole derivatives as potent thioredoxin reductase inhibitors that enhance the radiosensitivity of cancer cells

  摘要：

  Thioredoxin system is an attractive target to overcome radioresistance in cancer therapy. The redox enzyme thioredoxin reductase (TrxR) plays a vital role in restoring cellular thiol redox balance disrupted by radiation-induced reactive oxygens species (ROS) generation and oxidative damage. In this study, a series of 1,2,5-selenadiazoles have been synthesized and identified as highly effective inhibitors of TrxR to disrupt the intracellular redox balance, and thus significantly enhanced the sensitivity of cancer cells to X-ray. Upon irradiation, 1,2,5-selenadiazoles displayed a marked synergistic inhibitory effect on radioresistant A375 melanoma cell through enhancement of ROS overproduction, and subsequent induction of ROS-promoted apoptotic pathways, which triggered then mitochondrial dysfunction and caspase activation, finally resulted in augment of radiotherapeutic efficacy. Interestingly, we also found the interaction sites between 1,2,5-selenadiazole and the model peptide of TrxR, which can be confirmed by MALDI-ToF-MS. These results clearly demonstrate TrxR as a potential target for therapy of radioresistant cancers, and selenadiazole derivatives may be attractive radiosensitizing agent by targeting TrxR.

  DOI：

  10.1016/j.ejmech.2014.07.032

文献信息

• Selenadiazole derivatives as potent thioredoxin reductase inhibitors that enhance the radiosensitivity of cancer cells
  作者：Yuan-Wei Liang、Junsheng Zheng、Xiaoling Li、Wenjie Zheng、Tianfeng Chen

  DOI：10.1016/j.ejmech.2014.07.032

  日期：2014.9

  Thioredoxin system is an attractive target to overcome radioresistance in cancer therapy. The redox enzyme thioredoxin reductase (TrxR) plays a vital role in restoring cellular thiol redox balance disrupted by radiation-induced reactive oxygens species (ROS) generation and oxidative damage. In this study, a series of 1,2,5-selenadiazoles have been synthesized and identified as highly effective inhibitors of TrxR to disrupt the intracellular redox balance, and thus significantly enhanced the sensitivity of cancer cells to X-ray. Upon irradiation, 1,2,5-selenadiazoles displayed a marked synergistic inhibitory effect on radioresistant A375 melanoma cell through enhancement of ROS overproduction, and subsequent induction of ROS-promoted apoptotic pathways, which triggered then mitochondrial dysfunction and caspase activation, finally resulted in augment of radiotherapeutic efficacy. Interestingly, we also found the interaction sites between 1,2,5-selenadiazole and the model peptide of TrxR, which can be confirmed by MALDI-ToF-MS. These results clearly demonstrate TrxR as a potential target for therapy of radioresistant cancers, and selenadiazole derivatives may be attractive radiosensitizing agent by targeting TrxR.