(2Z,2'Z)-4,4'-[diselenodiylbis(benzene-4,1-diylimino)]bis(4-oxobut-2-enoic acid)

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2Z,2'Z)-4,4'-[diselenodiylbis(benzene-4,1-diylimino)]bis(4-oxobut-2-enoic acid)
• 英文别名: (Z)-4-[4-[[4-[[(Z)-3-carboxyprop-2-enoyl]amino]phenyl]diselanyl]anilino]-4-oxobut-2-enoic acid
• 化学式: C₂₀H₁₆N₂O₆Se₂
• 分子量: 538.277
• InChiKey: OKCSDWKTIQNPRL-HWAYABPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.12
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2Z,2'Z)-4,4'-[diselenodiylbis(benzene-4,1-diylimino)]bis(4-oxobut-2-enoic acid) 在 sodium acetate 作用下， 以 乙酸酐 为溶剂， 反应 3.0h， 以55.4%的产率得到1,1'-(diselenediyldibenzene-4,1-diyl)bis(1H-pyrrole-2,5-dione)
  参考文献：
  名称：

  Organoseleno cytostatic derivatives: Autophagic cell death with AMPK and JNK activation

  摘要：

  Selenocyanates and diselenides are potential antitumor agents. Here we report two series of selenium derivatives related to selenocyanates and diselenides containing carboxylic, amide and imide moieties. These compounds were screened for their potency and selectivity against seven tumor cell lines and two non-malignant cell lines. Results showed that MCF-7 cells were especially sensitive to the treatment, with seven compounds presenting GI(50) values below 10 mu M. Notably, the carboxylic selenocyanate 8b and the cyclic imide 10a also displayed high selectivity for tumor cells. Treatment of MCF-7 cells with these compounds resulted in cell cycle arrest at S phase, increased levels of pJNK and pAMPK and caspase independent cell death. Autophagy inhibitors wortmannin and chloroquine partially prevented 8b and 10a induced cell death. Consistent with autophagy, increased Beclinl and LC3-IIB and reduced SQSTM1/p62 levels were detected. Our results point to 8b and 10a as autophagic cell death inducers. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.04.074
• 作为产物：
  描述：

  马来酸酐 、 4-(4-氨基苯基)二硒基苯胺 以 甲苯 为溶剂， 反应 3.0h， 以91%的产率得到(2Z,2'Z)-4,4'-[diselenodiylbis(benzene-4,1-diylimino)]bis(4-oxobut-2-enoic acid)
  参考文献：
  名称：

  Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation

  摘要：

  Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multistressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans (C. albicans) fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.002

文献信息

• Organoselenocyanates and symmetrical diselenides redox modulators: Design, synthesis and biological evaluation
  作者：Saad Shaaban、Amr Negm、Mohamed A. Sobh、Ludger A. Wessjohann

  DOI：10.1016/j.ejmech.2015.05.002

  日期：2015.6

  Oxidative stress (OS) and disturbed intracellular redox balance have been predominantly observed in different types of cancer, including hepatocellular carcinoma (HCC). Agents which can stop OS multistressor events and modulate the intracellular redox state are becoming a major focus in HCC prevention. Among them, compounds with glutathione peroxidase (GPx)-like activity are of particularly concern. We herein report the synthesis of novel series of organoselenocyanates and symmetrical diselenide antioxidants, inspired by the natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants. Their cytotoxic activity was evaluated against Hep G2 cells and their antimicrobial activities were evaluated against Candida albicans (C. albicans) fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), gram-negative and gram-positive bacteria, respectively. These compounds were also tested for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage assays and a basic structure activity relationship was subsequently established. The physicochemical parameters and drug-likeness were computed employing the Molinspiration online property calculation toolkit and MolSoft software. Interestingly, some compounds proved to be more cytotoxic than ebselen and the known anticancer drug 5-Fu and in the same time they showed similar, sometime even more, antifungal activity than the reference antifungal drugs. Among these compounds, compound 16 was considered to be the most interesting with free radical-scavenging activity comparable to ascorbic acid and a GPx-like activity similar to ebselen. As most of these compounds comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Organoseleno cytostatic derivatives: Autophagic cell death with AMPK and JNK activation
  作者：Pablo Garnica、Ignacio Encío、Daniel Plano、Juan A. Palop、Carmen Sanmartín

  DOI：10.1016/j.ejmech.2019.04.074

  日期：2019.8

  Selenocyanates and diselenides are potential antitumor agents. Here we report two series of selenium derivatives related to selenocyanates and diselenides containing carboxylic, amide and imide moieties. These compounds were screened for their potency and selectivity against seven tumor cell lines and two non-malignant cell lines. Results showed that MCF-7 cells were especially sensitive to the treatment, with seven compounds presenting GI(50) values below 10 mu M. Notably, the carboxylic selenocyanate 8b and the cyclic imide 10a also displayed high selectivity for tumor cells. Treatment of MCF-7 cells with these compounds resulted in cell cycle arrest at S phase, increased levels of pJNK and pAMPK and caspase independent cell death. Autophagy inhibitors wortmannin and chloroquine partially prevented 8b and 10a induced cell death. Consistent with autophagy, increased Beclinl and LC3-IIB and reduced SQSTM1/p62 levels were detected. Our results point to 8b and 10a as autophagic cell death inducers. Published by Elsevier Masson SAS.