2-acetylpyridine-N,N-dimethylselenosemicarbazone | 79514-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-acetylpyridine-N,N-dimethylselenosemicarbazone
• 英文别名: 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone；(C5H4N)C(Me)NNHC(Se)(NMe2)；2-Acetylpyridine 4,4-dimethylselenosemicarbazone；N,N-dimethyl-N'-(1-pyridin-2-ylethylideneamino)carbamimidoselenoic acid
• CAS: 79514-49-1
• 化学式: C₁₀H₁₄N₄Se
• 分子量: 269.208
• InChiKey: XFYODGQDFXNBMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.52
• 氢给体数：
  1.0
• 氢受体数：
  4.0

制备方法与用途

Ap44mSe 是一种硒缩氨基脲，能够有效消耗细胞内的铁，导致转铁蛋白受体1上调、铁蛋白下调，并增加N-myc下游调节基因1的表达。此外，Ap44mSe 形成具有氧化还原活性的铜络合物，靶向溶酶体以诱导溶酶体膜通透性增强。

反应信息

• 作为反应物：
  描述：

  二丁基二氯化锡 、 2-acetylpyridine-N,N-dimethylselenosemicarbazone 在 NaOCH₃ 作用下， 以 甲醇 为溶剂， 以76%的产率得到
  参考文献：
  名称：

  某些含有吡啶基官能化硒代氨基甲磺酸钠配体的锡（IV）配合物的合成，结构，119 SnMössbauer光谱研究和生物活性

  摘要：

  含有吡啶基官能化硫基的一系列[Sn（L）ClR 2 ]类型的锡（IV）配合物（R：n Bu，Me，Cl; L：阴离子N，N，S或N，N，Se供体配体）制备了亚硒酸亚氨基氨基甲酸酯，并通过包括119 Sn和77 Se NMR光谱以及119 SnMössbauer光谱在内的光谱方法进行了全面表征。另外，几种衍生物的固态结构通过单晶X射线衍射确定。在体外，这些化合物的细胞毒性在三个不同的人类肿瘤细胞系进行了评价。IC 50 值在低nM范围内，最活泼的化合物是带有硒代氨基甲磺酸钠配体的三氯锡（IV）络合物。

  DOI：

  10.1016/j.jorganchem.2011.12.027
• 作为产物：
  描述：

  2-acetylpyridine 4,4-dimethylthiosemicarbazone 在 sodium hydroxide 、 sodium hydrogen selenide 作用下， 以 乙醇 为溶剂， 反应 40.08h， 生成 2-acetylpyridine-N,N-dimethylselenosemicarbazone
  参考文献：
  名称：

  Klayman; Scovill; Bartosevich, European Journal of Medicinal Chemistry, 1981, vol. 16, # 4, p. 317 - 320

  摘要：

  DOI：

文献信息

• Synthesis, structures and anti-malaria activity of some gold(i) phosphine complexes containing seleno- and thiosemicarbazonato ligands
  作者：Anja Molter、Jörg Rust、Christian W. Lehmann、Ganesh Deepa、Peter Chiba、Fabian Mohr

  DOI：10.1039/c1dt10885a

  日期：——

  A series of both mono- and dinuclear gold(I) phosphine complexes containing monoanionic seleno- and thiosemicarbazones as ligands were prepared and fully characterized by spectroscopic methods and, in some cases, by single crystal X-ray diffraction. The in vitro anti-malaria activity of some of these compounds was investigated in chloroquine sensitive strains of Plasmodium falciparum. The IC50 results

  制备了一系列含有单阴离子硒代和硫代半氨基甲酮作为配体的单核和双核金（I）膦配合物，并通过分光光度法（在某些情况下还通过单晶X射线衍射）进行了全面表征。在体外的这些化合物的一些抗疟疾活性进行了研究氯喹恶性疟原虫的敏感菌株。IC 50结果表明，含硫化合物的活性类似于氯喹，而硒衍生物仅表现出中等程度的抗疟疾活性。
• Synthesis, structures and reactivity of some mono- and dinuclear palladium(II) and platinum(II) complexes containing 2-pyridyl functionalised selenosemicarbazones
  作者：Anja Molter、Fabian Mohr

  DOI：10.1016/j.poly.2016.07.016

  日期：2016.12

  Abstract Mononuclear palladium(II) or platinum(II) complexes containing a 2-pyridyl-functionalised selenosemicarbazone ligand react with bis(diphenylphosphino)ethane in the presence of a silver salt affording dinuclear cationic compounds, in which the dppe bridges two metal centres. The solid-state structures of these compounds are discussed and possible reaction sequences leading to these products

  摘要含有2-吡啶基官能化亚硒键亚氨基配体的单核钯（II）或铂（II）配合物在银盐存在下与双（二苯基膦基）乙烷反应生成双核阳离子化合物，其中dppe桥接两个金属中心。讨论了这些化合物的固态结构，并给出了导致这些产物的可能的反应顺序。
• Synthesis, structures and reactivity of two oxidovanadium(IV) and dioxidovanadium(V) selenosemicarbazonato complexes
  作者：Anja Molter、Eckhard Bill、Fabian Mohr

  DOI：10.1016/j.inoche.2011.12.031

  日期：2012.3

  Abstract The preparation as well as spectroscopic and structural characterization of some oxovanadium(IV) and dioxovanadium(V) complexes containing deprotonated selenosemicarbazone ligands is reported.

  摘要 报道了一些含去质子化硒化碳腙配体的氧钒 (IV) 和二氧钒 (V) 配合物的制备以及光谱和结构表征。
• Indium(iii), antimony(iii) and bismuth(iii) dihalide complexes with tridentate, anionic thio- and selenosemicarbazonato ligands
  作者：Anja Molter、Fabian Mohr

  DOI：10.1039/c0dt01693d

  日期：——

  Some indium(III), antimony(III) and bismuth(III) dihalide complexes containing deprotonated, tridentate thio- and selenosemicarbazone ligands were prepared and were fully characterized by spectroscopic methods. In addition, the crystal structures of some of the compounds were obtained. TGA and DSC analyses were carried out on selected samples to assess their suitability as single-molecule precursors

  制备了一些含有去质子的，三齿的硫代和亚硒酰胺基氨基甲酸酯配体的铟（III），锑（III）和铋（III）二卤化物配合物，并通过光谱法对其进行了全面表征。另外，获得了某些化合物的晶体结构。对选定的样品进行了TGA和DSC分析，以评估它们作为金属硒化物纳米材料的单分子前体的适用性。
• Novel Mechanism of Cytotoxicity for the Selective Selenosemicarbazone, 2-Acetylpyridine 4,4-Dimethyl-3-selenosemicarbazone (Ap44mSe): Lysosomal Membrane Permeabilization
  作者：Zaynab Al-Eisawi、Christian Stefani、Patric J. Jansson、Akanksha Arvind、Philip C. Sharpe、Maram T. Basha、George M. Iskander、Naresh Kumar、Zaklina Kovacevic、Darius J. R. Lane、Sumit Sahni、Paul V. Bernhardt、Des R. Richardson、Danuta S. Kalinowski

  DOI：10.1021/acs.jmedchem.5b01399

  日期：2016.1.14

  Selenosemicarbazones show marked antitumor activity. However, their mechanism of action remains unknown. We examined the medicinal chemistry of the selenosemicarbazone, 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone (Ap44mSe), and its iron and copper complexes to elucidate its mechanisms of action. Ap44mSe demonstrated a pronounced improvement in selectivity toward neoplastic relative to normal cells compared to its parent thiosemicarbazone. It also effectively depleted cellular Fe, resulting in transferrin receptor-1 up-regulation, ferritin down-regulation, and increased expression of the potent metastasis suppressor, N-myc downstream regulated gene-1. Significantly, Ap44mSe limited deleterious methemoglobin formation, highlighting its usefulness in overcoming toxicities of clinically relevant thiosemicarbazones. Furthermore, Cu-Ap44mSe mediated intracellular reactive oxygen species generation, which was attenuated by the antioxidant, N-acetyl-l-cysteine, or Cu sequestration. Notably, Ap44mSe forms redox active Cu complexes that target the lysosome to induce lysosomal membrane permeabilization. This investigation highlights novel structure-activity relationships for future chemotherapeutic design and underlines the potential of Ap44mSe as a selective anticancer/antimetastatic agent.