1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol | 59157-24-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol
• 英文别名: (E)-2-((2-hydroxynaphthalen-1-yl)methylene)-N-phenylhydrazinecarbothioamide；N4pT；2-hydroxy-1-naphthaldehyde-N(4)-phenylthiosemicarbazone；2-hydroxy-1-naphthaldehyde N-phenylthiosemicarbazone；1-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]-3-phenylthiourea
• CAS: 59157-24-3；663617-20-7
• 化学式: C₁₈H₁₅N₃OS
• 分子量: 321.403
• InChiKey: RISBHRGHXBAQJW-XDHOZWIPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol 、 copper diacetate 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper–thiosemicarbazone complexes

  摘要：

  The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts.

  DOI：

  10.1007/s00775-016-1350-2
• 作为产物：
  描述：

  4-苯基-3-硫代氨基脲 、 2-羟基-1-萘甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以81%的产率得到1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol
  参考文献：
  名称：

  缩氨基硫脲的体外抗氧化、抗炎和硅分子对接研究

  摘要：

  摘要 5-甲氧基水杨醛/2-羟基-1-萘醛与(un)反应得到了一系列5-甲氧基水杨醛附加氨基硫脲(1-4)和2-羟基-1-萘醛附加氨基硫脲(5-8)。氨基硫脲衍生物的 N 末端位置的取代变化所带来的生物学特性。通过元素分析和各种光谱技术（紫外-可见光、红外光谱、核磁共振和质谱）对化合物进行了全面表征。三种化合物（1、2 和 7）的固态结构通过单晶 X 射线衍射法测定。化合物(1、2和7)采用具有P21/c(1和2)或C2/c(7)空间群的单斜晶系。分别通过体外 DPPH 和溶血试验分析了化合物 (1-8) 的抗氧化和非溶血活性。抗炎潜力通过体外 PLA2 抑制试验和计算机分子对接研究得到验证。体外和计算机研究揭示了缩氨基硫脲衍生物有希望的抗炎潜力。化合物 2、4、6、7 和 8 显示出显着的抗炎活性。

  DOI：

  10.1016/j.molstruc.2017.05.054

文献信息

• Four cytotoxic N4-substituted thiosemicarbazones derived from 2-hydroxynaphthalene-1-carboxaldehyde
  作者：Paul V. Bernhardt、Lorraine M. Caldwell、David B. Lovejoy、Des R. Richardson

  DOI：10.1107/s0108270103021401

  日期：2003.11.1

  The X-ray crystal structures are reported of four novel and potentially O,N,S-tridentate donor ligands that demonstrate antitumour activity. These ligands are 1-[(4-methylthiosemicarbazono)methyl]-2-naphthol, C₁₃H₁₃N₃OS, (III), 1-[(4-ethylthiosemicarbazono)methyl]-2-naphthol, C₁₄H₁₅N₃OS, (IV), 1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol, C₁₈H₁₅N₃OS, (V), and 1-[(4,4-dimethylthiosemicarbazono)methyl]-2-naphthol dimethyl sulfoxide solvate, C₁₄H₁₅N₃OS·C₂H₆OS, (VI). These chelators are N4-substituted thiosemicarbazones, each based on the same parent aldehyde, namely 2-zhydroxynaphthalene-1-carboxaldehyde isonicotinoylhydrazone. Conformational variations within this series are discussed in relation to the optimum conformation for metal-ion binding.

  报告了四种新型和潜在的 O、N、S-三叉供体配体的 X 射线晶体结构，这些配体具有抗肿瘤活性。这些配体是 1-[(4-甲基硫代氨基羰基)甲基]-2-萘酚，C13H13N3OS，(III)；1-[(4-乙基硫代氨基羰基)甲基]-2-萘酚，C14H15N3OS，(IV)、1-[（4-苯基thiosemicarbazono）甲基]-2-萘酚，C18H15N3OS，（V），以及 1-[（4,4-二甲基thiosemicarbazono）甲基]-2-萘酚二甲亚砜溶液，C14H15N3OS-C2H6OS，（VI）。这些螯合剂都是 N4 取代的硫代氨基甲酰肼，每一种都基于相同的母醛，即 2-氮羟基萘-1-甲醛异烟酰腙。该系列中的构象变化与金属离子结合的最佳构象有关。
• Novel thiosemicarbazone derivatives as potential antitumor agents: Synthesis, physicochemical and structural properties, DNA interactions and antiproliferative activity
  作者：Ivica Đilović、Mirta Rubčić、Višnja Vrdoljak、Sandra Kraljević Pavelić、Marijeta Kralj、Ivo Piantanida、Marina Cindrić

  DOI：10.1016/j.bmc.2008.03.006

  日期：2008.5

  The paper describes synthesis of several novel thiosemicarbazone derivatives. Furthermore, crystal and molecular structure of 4-diethylamino-salicylaldehyde 4-phenylthiosemicarbazone revealed planarity of conjugated aromatic system, which suggested the possibility of DNA binding by intercalation, especially for here studied naphthalene derivatives. However, here presented DNA binding studies excluded

  该论文描述了几种新型硫代半碳酰胺衍生物的合成。此外，4-二乙基氨基-水杨醛4-苯基硫代半脲的晶体和分子结构揭示了共轭芳族体系的平面性，这暗示了通过嵌入特别是对于本文研究的萘衍生物而言，DNA结合的可能性。但是，这里提出的DNA结合研究排除了这种作用方式。将新型衍生物的理化和结构性质与先前研究的类似物（作为参考化合物）进行比较，揭示出明显的差异。此外，新的硫代半脲衍生物（1、2和5-8）在五个肿瘤细胞系上的抗增殖活性明显高于参考化合物3和4，这支持了它们作为潜在抗肿瘤剂的进一步研究。
• Mitochondrial lipid permeable iron chelators for treating and preventing ischemia/reperfusion (I/R) injury in the heart following an ischemic event
  申请人：Northwestern University

  公开号：US10258612B2

  公开（公告）日：2019-04-16

  Disclosed are methods and compositions for treating or preventing a disease or disorder responsive to a decrease in baseline mitochondrial iron in a subject in need thereof. The methods typically include administering a pharmaceutical composition comprising a mitochondrial permeable iron chelator to the subject.

  本发明公开了治疗或预防疾病或失调的方法和组合物，这些疾病或失调对有需要的受试者线粒体基线铁的减少有反应。这些方法通常包括向受试者施用包含线粒体可渗透铁螯合剂的药物组合物。
• Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper–thiosemicarbazone complexes
  作者：Fady N. Akladios、Scott D. Andrew、Christopher J. Parkinson

  DOI：10.1007/s00775-016-1350-2

  日期：2016.6

  The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts.
• IRON CHELATORS FOR TREATING AND PREVENTING CELL DEATH AND ORGAN DAMAGE FOLLOWING AN ISCHEMIC EVENT
  申请人：Northwestern University

  公开号：US20170014397A1

  公开（公告）日：2017-01-19

  Disclosed are methods and compositions for treating or preventing a disease or disorder responsive to a decrease in baseline mitochondrial iron in a subject in need thereof. The methods typically include administering a pharmaceutical composition comprising a mitochondrial permeable iron chelator to the subject.