2'-(4''-chlorobenzoyl)pyridine thiosemicarbazone | 1334897-81-2

• 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: 2'-(4''-chlorobenzoyl)pyridine thiosemicarbazone
• 英文别名: [[(4-chlorophenyl)-pyridin-2-ylmethylidene]amino]thiourea
• CAS: 1334897-81-2
• 化学式: C₁₃H₁₁ClN₄S
• 分子量: 290.776
• InChiKey: UCJHHOJZALJYHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (4-氯苯基)(2-吡啶基)甲酮 、 氨基硫脲 在 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 以82%的产率得到2'-(4''-chlorobenzoyl)pyridine thiosemicarbazone
  参考文献：
  名称：

  Halogenated 2′-Benzoylpyridine Thiosemicarbazone (XBpT) Chelators with Potent and Selective Anti-Neoplastic Activity: Relationship to Intracellular Redox Activity

  摘要：

  Iron chelators of the 2'-benzoylpyridine thiosemicarbazone (BpT) class show substantial potential as anticancer agents. To explore structure activity relationships, new BpT analogues were designed that incorporated halogen substituents on the noncoordinating phenyl group (XBpTs). These XBpT ligands exhibited potent antiproliferative activity with some analogues exceeding that of the parent BpT compound. Importantly, there was an appreciable therapeutic index in vitro, as mortal cells were significantly less affected by these chelators relative to neoplastic cells. The addition of a halogen led to a halogen-specific increase in the redox potential of XBpT Fe complexes. Probing for chelator-induced intracellular reactive oxygen species (ROS) with the fluorescent probe, 2',7'-dichlorofluorescein, revealed a 1.5-4.7-fold increase in fluorescence upon incorporation of Cl, Br, or I to the parent analogues. Furthermore, an important structure-activity relationship was deduced where the addition of halogens led to a positive correlation between intracellular ROS generation and antiproliferative activity in the more hydrophilic BpT parent compounds.

  DOI：

  10.1021/jm200924c

文献信息

• Halogenated 2′-Benzoylpyridine Thiosemicarbazone (XBpT) Chelators with Potent and Selective Anti-Neoplastic Activity: Relationship to Intracellular Redox Activity
  作者：Christian Stefani、Gaya Punnia-Moorthy、David B. Lovejoy、Patric J. Jansson、Danuta S. Kalinowski、Philip C. Sharpe、Paul V. Bernhardt、Des R. Richardson

  DOI：10.1021/jm200924c

  日期：2011.10.13

  Iron chelators of the 2'-benzoylpyridine thiosemicarbazone (BpT) class show substantial potential as anticancer agents. To explore structure activity relationships, new BpT analogues were designed that incorporated halogen substituents on the noncoordinating phenyl group (XBpTs). These XBpT ligands exhibited potent antiproliferative activity with some analogues exceeding that of the parent BpT compound. Importantly, there was an appreciable therapeutic index in vitro, as mortal cells were significantly less affected by these chelators relative to neoplastic cells. The addition of a halogen led to a halogen-specific increase in the redox potential of XBpT Fe complexes. Probing for chelator-induced intracellular reactive oxygen species (ROS) with the fluorescent probe, 2',7'-dichlorofluorescein, revealed a 1.5-4.7-fold increase in fluorescence upon incorporation of Cl, Br, or I to the parent analogues. Furthermore, an important structure-activity relationship was deduced where the addition of halogens led to a positive correlation between intracellular ROS generation and antiproliferative activity in the more hydrophilic BpT parent compounds.