2-(4-Benzylpiperazin-1-YL)-N'-[(Z)-(2-chlorophenyl)methylidene]acetohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(4-Benzylpiperazin-1-YL)-N'-[(Z)-(2-chlorophenyl)methylidene]acetohydrazide
• 英文别名: 2-(4-benzylpiperazin-1-yl)-N-[(Z)-(2-chlorophenyl)methylideneamino]acetamide
• 化学式: C₂₀H₂₃ClN₄O
• 分子量: 370.882
• InChiKey: VOJWBWSQEOGCSO-HMAPJEAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯苯甲醛 、 4-(苯甲基)-1-哌嗪乙酸 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 2-(4-Benzylpiperazin-1-YL)-N'-[(Z)-(2-chlorophenyl)methylidene]acetohydrazide 、 2-(4-benzyl-1-piperazinyl)-N'-[(E)-(2-chlorophenyl)methylidene]acetohydrazide
  参考文献：
  名称：

  Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3

  摘要：

  A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound I (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.

  DOI：

  10.1021/jm900722z

文献信息

• Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3
  作者：Quinn P. Peterson、Danny C. Hsu、David R. Goode、Chris J. Novotny、Ryan K. Totten、Paul J. Hergenrother

  DOI：10.1021/jm900722z

  日期：2009.9.24

  A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound I (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.