N-methyl-2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbothioamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-methyl-2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbothioamide
• 英文别名: 2-(4-N-methyl-3-thiosemicarbazone)-8-hydroxyquinoline；1-[(E)-(8-hydroxyquinolin-2-yl)methylideneamino]-3-methylthiourea
• 化学式: C₁₂H₁₂N₄OS
• 分子量: 260.319
• InChiKey: PSIOFESDVILJSE-VGOFMYFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  8-羟基喹啉-2-甲醛	2-formyl oxine	14510-06-6	C10H7NO2	173.171

反应信息

• 作为反应物：
  描述：

  copper(II) acetate monohydrate 、 N-methyl-2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbothioamide 以 N,N-二甲基甲酰胺 为溶剂， 以92%的产率得到(2-(4-N-methyl-3-thiosemicarbazonato)-8-quinolinolato)copper(II)
  参考文献：
  名称：

  Copper(ii) complexes of hybrid hydroxyquinoline-thiosemicarbazone ligands: GSK3β inhibition due to intracellular delivery of copper

  摘要：

  与阿尔茨海默病相关的认知衰退似乎与糖原合酶激酶3β（GSK3β）活性增强导致蛋白tau的高度磷酸化，从而形成神经毒性神经原纤维缠结有关。异常的金属离子稳态，特别是涉及铜的部分，已隐含地与该疾病的病理机制相关联。发现增加细胞内铜浓度会触发导致GSK3β抑制的途径。本文介绍了四齿杂化羟基喹啉-缩硫半卡巴脘前配体的合成与表征。这些配体能与CuII形成稳定的配合物，其中铜离子为四配位且基本呈平面正方形，这一特点通过单晶X射线晶体学进行了表征。通过电化学技术研究了金属离子的还原为CuI的过程，并且发生在允许细胞内还原的电位。这些新的配合物在类神经细胞SH-SY5Y中表现出依赖类型的细胞膜透过性，随后增加了细胞内铜浓度。增加的细胞内铜导致了剂量依赖性的GSK3β抑制（磷酸化）。

  DOI：

  10.1039/c0dt01176b
• 作为产物：
  描述：

  8-羟基喹啉-2-甲醛 、 4-甲基氨基硫脲 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.2h， 生成 N-methyl-2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbothioamide
  参考文献：
  名称：

  Investigation of the Biological Properties of (Hetero)Aromatic Thiosemicarbazones

  摘要：

  采用微波辅助法设计并合成了两系列基于硫代 semicarbazone 的铁螯合剂（共 27 个化合物）。根据相似性搜索，以喹啉和卤代苯为母体骨架。通过 HPLC 测量并计算所合成化合物的亲脂性。对所合成的化合物进行了针对八种病原真菌的初级体外筛选。仅有少数化合物显示出中等的抗真菌活性，其中(E)-2-(喹啉-2-基乙烯基)-N,N-二甲基胼硫代卡巴脒对大部分测试的真菌株的抗真菌活性均优于氟康唑。采用人结肠癌细胞系(HCT-116) 测量其抗增殖活性。部分测试化合物显示出亚微摩尔级的抗增殖活性。此外，还测试了它们抑制菠菜（Spinacia oleracea L.）叶绿体中光合电子传递（PET）的能力。对于所有化合物，讨论了其结构-活性关系。

  DOI：

  10.3390/molecules171113483

文献信息

• Investigation of the Biological Properties of (Hetero)Aromatic Thiosemicarbazones
  作者：Maciej Serda、Anna Mrozek-Wilczkiewicz、Josef Jampilek、Matus Pesko、Katarina Kralova、Marcela Vejsova、Robert Musiol、Alicja Ratuszna、Jaroslaw Polanski

  DOI：10.3390/molecules171113483

  日期：——

  Two series of thiosemicarbazone-based iron chelators (twenty-seven compounds) were designed and synthesized using a microwave-assisted approach. Quinoline and halogenated phenyl were selected as parent scaffolds on the basis of a similarity search. The lipophilicity of the synthesized compounds was measured using HPLC and then calculated. Primary in vitro screening of the synthesized compounds was performed against eight pathogenic fungal strains. Only a few compounds showed moderate activity against fungi, and (E)-2-(quinolin-2-ylvinyl)-N,N-dimethylhydrazine-carbothioamide appeared to be more effective than fluconazole against most of the fungal strains tested. Antiproliferative activity was measured using a human colon cancer cell line (HCT-116). Several of the tested compounds showed submicromolar antiproliferative activity. Compounds were also tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The structure-activity relationships are discussed for all of the compounds.

  采用微波辅助法设计并合成了两系列基于硫代 semicarbazone 的铁螯合剂（共 27 个化合物）。根据相似性搜索，以喹啉和卤代苯为母体骨架。通过 HPLC 测量并计算所合成化合物的亲脂性。对所合成的化合物进行了针对八种病原真菌的初级体外筛选。仅有少数化合物显示出中等的抗真菌活性，其中(E)-2-(喹啉-2-基乙烯基)-N,N-二甲基胼硫代卡巴脒对大部分测试的真菌株的抗真菌活性均优于氟康唑。采用人结肠癌细胞系(HCT-116) 测量其抗增殖活性。部分测试化合物显示出亚微摩尔级的抗增殖活性。此外，还测试了它们抑制菠菜（Spinacia oleracea L.）叶绿体中光合电子传递（PET）的能力。对于所有化合物，讨论了其结构-活性关系。
• Synthesis and characterization of quinoline-based thiosemicarbazones and correlation of cellular iron-binding efficacy to anti-tumor efficacy
  作者：Maciej Serda、Danuta S. Kalinowski、Anna Mrozek-Wilczkiewicz、Robert Musiol、Agnieszka Szurko、Alicja Ratuszna、Namfon Pantarat、Zaklina Kovacevic、Angelica M. Merlot、Des R. Richardson、Jaroslaw Polanski

  DOI：10.1016/j.bmcl.2012.07.030

  日期：2012.9

  Iron chelators have emerged as a potential anti-cancer treatment strategy. In this study, a series of novel thiosemicarbazone iron chelators containing a quinoline scaffold were synthesized and characterized. A number of analogs show markedly greater anti-cancer activity than the 'gold-standard' iron chelator, desferrioxamine. The anti-proliferative activity and iron chelation efficacy of several of these ligands (especially compound 1b), indicates that further investigation of this class of thiosemicarbazones is worthwhile. (C) 2012 Elsevier Ltd. All rights reserved.
• Copper(<scp>ii</scp>) complexes of hybrid hydroxyquinoline-thiosemicarbazone ligands: GSK3β inhibition due to intracellular delivery of copper
  作者：James L. Hickey、Peter J. Crouch、Sithorn Mey、Aphrodite Caragounis、Jonathan M White、Anthony R. White、Paul S. Donnelly

  DOI：10.1039/c0dt01176b

  日期：——

  Cognitive decline associated with Alzheimer's disease appears to be related to the hyper-phosphorylation of the protein tau as a consequence of increased activity of glycogen synthase kinase 3β (GSK3β), and subsequent formation of neurotoxic neurofibrillary tangles. Abberant metal ion homeostasis, particularly involving copper has been implicitly linked to the pathogenesis of the disease. Increasing intracellular copper concentrations has been found to trigger pathways that result in inhibition of GSK3β. The syntheses and characterisation of tetradentate hybrid hydroxyquinoline-thiosemicarbazone proligands is presented. The ligands form stable complexes with CuII where the copper ion is four coordinate and essentially square planar as characterised by single crystal X-ray crystallography. The reduction of the metal ion to CuI has been studied by electrochemical techniques and occurs at potentials that permit intracellular reduction. The new complexes show class dependent cell membrane permeability in neuronal-like SH-SY5Y cells with subsequent increases in intracellular copper concentrations. The increased intracellular copper results in a dose-dependent inhibition (phosphorylation) of GSK3β.

  与阿尔茨海默病相关的认知衰退似乎与糖原合酶激酶3β（GSK3β）活性增强导致蛋白tau的高度磷酸化，从而形成神经毒性神经原纤维缠结有关。异常的金属离子稳态，特别是涉及铜的部分，已隐含地与该疾病的病理机制相关联。发现增加细胞内铜浓度会触发导致GSK3β抑制的途径。本文介绍了四齿杂化羟基喹啉-缩硫半卡巴脘前配体的合成与表征。这些配体能与CuII形成稳定的配合物，其中铜离子为四配位且基本呈平面正方形，这一特点通过单晶X射线晶体学进行了表征。通过电化学技术研究了金属离子的还原为CuI的过程，并且发生在允许细胞内还原的电位。这些新的配合物在类神经细胞SH-SY5Y中表现出依赖类型的细胞膜透过性，随后增加了细胞内铜浓度。增加的细胞内铜导致了剂量依赖性的GSK3β抑制（磷酸化）。