N-cyclohexyl-2-(3-ethoxy-2-hydroxybenzylidene)hydrazine-1-carbothiamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-cyclohexyl-2-(3-ethoxy-2-hydroxybenzylidene)hydrazine-1-carbothiamide
• 英文别名: 3-ethoxysalicylaldehyde cyclohexylthiosemicarbazone；3‑ethoxysalicylaldehyde‑N4‑cyclohexylthiosemicarbazone；3-Ethoxysalicylaldehyde-n4-cyclohexylthiosemicarbazone；1-cyclohexyl-3-[(3-ethoxy-2-hydroxyphenyl)methylideneamino]thiourea
• 化学式: C₁₆H₂₃N₃O₂S
• 分子量: 321.444
• InChiKey: AOBPGNQBGUEOBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  98
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  copper(II) acetate monohydrate 、 N-cyclohexyl-2-(3-ethoxy-2-hydroxybenzylidene)hydrazine-1-carbothiamide 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以66%的产率得到[Cu₂(esct)₂]_n
  参考文献：
  名称：

  铜 (II) 配合物作为新型抗癌药物：合成、光谱研究、晶体结构、计算机分子对接和细胞毒性

  摘要：

  合成了三种新型铜的混合配体配合物，衍生自母体环己基氨基硫脲，以及 2-甲基吡啶和 5,5'-二甲基联吡啶等二级配体。它们的特点是元素分析、光谱技术（IR、UV-vis）和 X 射线晶体学。单晶 X 射线结构表明配合物1具有扭曲的方形棱锥几何形状，配合物2具有扭曲的方形平面几何形状。配合物3是一维聚合物。通过吸收光谱滴定和荧光测量研究了复合物与 CT-DNA 的相互作用。观察到的数据表明，复合物通过与 CT-DNA 结合一种嵌入的结合方式。通过凝胶电泳研究了合成化合物的有效 ​​PTZ57R (bp: 2886) 裂解能力。进行了与相应 DNA 蛋白的 Cu(II) 复合物的分子对接研究。对 MDA-MB-231 乳腺癌细胞系进行了该复合物的体外细胞毒性研究。

  DOI：

  10.1016/j.molstruc.2022.132672
• 作为产物：
  描述：

  3-乙氧基水杨醛 、 4-环己基-3-硫代氨基脲 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 以98%的产率得到N-cyclohexyl-2-(3-ethoxy-2-hydroxybenzylidene)hydrazine-1-carbothiamide
  参考文献：
  名称：

  Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives

  摘要：

  In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.

  DOI：

  10.1016/j.bioorg.2020.103924

文献信息

• Copper(II) complexes as novel anticancer drug: Synthesis, spectral studies, crystal structures, in silico molecular docking and cytotoxicity
  作者：Nimya Ann Mathews、M.R. Prathapachandra Kurup

  DOI：10.1016/j.molstruc.2022.132672

  日期：2022.6

  Three novel mixed ligand complexes of copper, derived from the parent cyclohexylthiosemicarbazones were synthesized along with the secondary ligands such as 2-picoline and 5,5’-dimethylbipyridine. They are characterised by elemental analysis, spectroscopic techniques (IR, UV-vis) and X-ray crystallography. The single crystal X-ray structure showed that the complex 1 is having distorted square pyramidal

  合成了三种新型铜的混合配体配合物，衍生自母体环己基氨基硫脲，以及 2-甲基吡啶和 5,5'-二甲基联吡啶等二级配体。它们的特点是元素分析、光谱技术（IR、UV-vis）和 X 射线晶体学。单晶 X 射线结构表明配合物1具有扭曲的方形棱锥几何形状，配合物2具有扭曲的方形平面几何形状。配合物3是一维聚合物。通过吸收光谱滴定和荧光测量研究了复合物与 CT-DNA 的相互作用。观察到的数据表明，复合物通过与 CT-DNA 结合一种嵌入的结合方式。通过凝胶电泳研究了合成化合物的有效 ​​PTZ57R (bp: 2886) 裂解能力。进行了与相应 DNA 蛋白的 Cu(II) 复合物的分子对接研究。对 MDA-MB-231 乳腺癌细胞系进行了该复合物的体外细胞毒性研究。
• Metal Complexes of a Thiosemicarbazone with Heterocyclic Bases as Coligands: Spectral Characterization, Crystal Structures, DFT and In silico Docking Studies
  作者：Nimya Ann Mathews、M. Sithambaresan、Savaş Kaya、Samir Chtita、M. R. Prathapachandra Kurup

  DOI：10.1007/s10870-023-01001-2

  日期：2024.3

  thiosemicarbazone derivative (H2esct) along with heterocyclic bases. The thiosemicarbazone forms doubly deprotonated anions in all the complexes to coordinate via thiolate S, azomethine N and phenolate O atoms. The complexes were characterized by various spectroscopic techniques like infrared, UV–vis, 1H NMR and EPR spectra. The single crystal XRD studies confirmed the structures. All the three complexes got crystallized

  铜(II)和锌(II)络合物, [Cu(esct)(4-pico)] ( 1 ), [Zn(esct)(5,5′-dmbipy)]·H 2 O ( 2 ), [Cu (esct)(5,5'-dmbipy)] ( 3 ), (其中H 2 esct = 3-乙氧基水杨醛-N 4 -环己基缩氨基硫脲)通过乙酸铜/乙酸锌与缩氨基硫脲衍生物(H 2 esct)反应合成具有杂环碱基。缩氨基硫脲在所有配合物中形成双去质子化阴离子，通过硫醇盐 S、甲亚胺 N 和酚盐 O 原子进行配位。通过各种光谱技术对配合物进行了表征，如红外、紫外-可见、1 H NMR 和 EPR 光谱。单晶 XRD 研究证实了该结构。所有三种配合物均在三斜空间群P \(\overline1 }.\)中结晶，发现配合物在金属中心周围有四、五和六配位。赫什菲尔德表面分析解释了范德华相互作用在其中的重要性。我们使用密度泛函理论 (DFT)
• Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives
  作者：Muhammad Ishaq、Parham Taslimi、Zahid Shafiq、Samra Khan、Ramin Ekhteiari Salmas、Mohammad Mahdi Zangeneh、Aamer Saeed、Akram Zangeneh、Nastaran Sadeghian、Asnuzilawati Asari、Habsah Mohamad

  DOI：10.1016/j.bioorg.2020.103924

  日期：2020.7

  In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.