2-[(5-Bromo-2,3-dioxoindol-1-yl)methyl]benzonitrile | 1021049-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-[(5-Bromo-2,3-dioxoindol-1-yl)methyl]benzonitrile
• CAS: 1021049-12-6
• 化学式: C₁₆H₉BrN₂O₂
• 分子量: 341.164
• InChiKey: KYPCQZWUERVNGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(5-Bromo-2,3-dioxoindol-1-yl)methyl]benzonitrile 、 苯甲酰肼 在 溶剂黄146 作用下， 反应 6.0h， 生成
  参考文献：
  名称：

  Antiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-Mediated Suppression of Cap-Independent Translation

  摘要：

  We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infection significantly reduced viral particle formation, resulting in protection of cells from virus-induced apoptosis. In addition, ID45 treatment caused remarkable. up-regulation of glucose-regulated protein 78 (GRP78), a hallmark of endoplasmic reticulum (ER) stress and an indicator of enhanced cell viability. In identifying the ER stress response pathway induced by ID45, we found that ID45 activated PKR-like ER protein kinase (PERK) but failed to up-regulate eIF2 alpha phosphorylation. Instead ID45 activated transcription factor Nrf2 (NF-E2-related factor-2), which is evidenced by its nuclear translocation and upregulation of its downstream target genes NQO1 (NAD(P)H quinone-oxidoreductase 1) and GCLM (glutamate:cysteine ligase, modifier subunit). This observation was further verified by using siRNAs of GRP78 or Nrf2, which blocked both the translocation of Nrf2 and up-regulation of its target genes, leading to aggressive viral replication and enhanced cell apoptosis. Finally, we found that ID45-induced up-regulation of NQO1 protected. eIF4GI, a. eukaryotic cap-dependent translation initiation factor, from cleavage by CVB3 protease and degradation by proteasomes. Taken together, our findings established that a novel antiviral mechanism of isatin derivative 1045 inhibits CVB3 replication by promoting cell survival through a PERK/Nrf2-dependent ER stress pathway, which benefits host cap-dependent translation but suppresses CVB3 cap-independent translation.

  DOI：

  10.1021/cb400775z
• 作为产物：
  描述：

  5-溴靛红 、 邻氰基氯苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-[(5-Bromo-2,3-dioxoindol-1-yl)methyl]benzonitrile
  参考文献：
  名称：

  Antiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-Mediated Suppression of Cap-Independent Translation

  摘要：

  We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infection significantly reduced viral particle formation, resulting in protection of cells from virus-induced apoptosis. In addition, ID45 treatment caused remarkable. up-regulation of glucose-regulated protein 78 (GRP78), a hallmark of endoplasmic reticulum (ER) stress and an indicator of enhanced cell viability. In identifying the ER stress response pathway induced by ID45, we found that ID45 activated PKR-like ER protein kinase (PERK) but failed to up-regulate eIF2 alpha phosphorylation. Instead ID45 activated transcription factor Nrf2 (NF-E2-related factor-2), which is evidenced by its nuclear translocation and upregulation of its downstream target genes NQO1 (NAD(P)H quinone-oxidoreductase 1) and GCLM (glutamate:cysteine ligase, modifier subunit). This observation was further verified by using siRNAs of GRP78 or Nrf2, which blocked both the translocation of Nrf2 and up-regulation of its target genes, leading to aggressive viral replication and enhanced cell apoptosis. Finally, we found that ID45-induced up-regulation of NQO1 protected. eIF4GI, a. eukaryotic cap-dependent translation initiation factor, from cleavage by CVB3 protease and degradation by proteasomes. Taken together, our findings established that a novel antiviral mechanism of isatin derivative 1045 inhibits CVB3 replication by promoting cell survival through a PERK/Nrf2-dependent ER stress pathway, which benefits host cap-dependent translation but suppresses CVB3 cap-independent translation.

  DOI：

  10.1021/cb400775z

文献信息

• Antiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-Mediated Suppression of Cap-Independent Translation
  作者：Huifang M. Zhang、Huanqin Dai、Paul J. Hanson、Huidong Li、Hui Guo、Xin Ye、Maged G. Hemida、Luoqiang Wang、Yaojun Tong、Ye Qiu、Selina Liu、Fengping Wang、Fuhang Song、Buchang Zhang、Jian-Guo Wang、Li-Xin Zhang、Decheng Yang

  DOI：10.1021/cb400775z

  日期：2014.4.18

  We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infection significantly reduced viral particle formation, resulting in protection of cells from virus-induced apoptosis. In addition, ID45 treatment caused remarkable. up-regulation of glucose-regulated protein 78 (GRP78), a hallmark of endoplasmic reticulum (ER) stress and an indicator of enhanced cell viability. In identifying the ER stress response pathway induced by ID45, we found that ID45 activated PKR-like ER protein kinase (PERK) but failed to up-regulate eIF2 alpha phosphorylation. Instead ID45 activated transcription factor Nrf2 (NF-E2-related factor-2), which is evidenced by its nuclear translocation and upregulation of its downstream target genes NQO1 (NAD(P)H quinone-oxidoreductase 1) and GCLM (glutamate:cysteine ligase, modifier subunit). This observation was further verified by using siRNAs of GRP78 or Nrf2, which blocked both the translocation of Nrf2 and up-regulation of its target genes, leading to aggressive viral replication and enhanced cell apoptosis. Finally, we found that ID45-induced up-regulation of NQO1 protected. eIF4GI, a. eukaryotic cap-dependent translation initiation factor, from cleavage by CVB3 protease and degradation by proteasomes. Taken together, our findings established that a novel antiviral mechanism of isatin derivative 1045 inhibits CVB3 replication by promoting cell survival through a PERK/Nrf2-dependent ER stress pathway, which benefits host cap-dependent translation but suppresses CVB3 cap-independent translation.