N'-benzylidene-1H-indole-2-carbohydrazide | 15315-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N'-benzylidene-1H-indole-2-carbohydrazide
• 英文别名: indole-2-carboxylic acid benzylidenehydrazide；Benzaldehyd-2-indoloylhydrazon；Indole-2-carboxylic acid benzylidene-hydrazide；N-(benzylideneamino)-1H-indole-2-carboxamide
• CAS: 15315-50-1
• 化学式: C₁₆H₁₃N₃O
• 分子量: 263.299
• InChiKey: SYUQFFCOGGAGKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 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：
  57.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氯甲酸乙酯 、 N'-benzylidene-1H-indole-2-carbohydrazide 在 三乙胺 作用下， 以 氯仿 为溶剂， 以90%的产率得到ethyl 2-[(benzylideneamino)carbamoyl]indole-1-carboxylate
  参考文献：
  名称：

  Monge, A.; Palop, J. A.; Tabar, P., Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 397 - 400

  摘要：

  DOI：
• 作为产物：
  描述：

  吲哚-2-羧酸 在 硫酸 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 N'-benzylidene-1H-indole-2-carbohydrazide
  参考文献：
  名称：

  Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein

  摘要：

  癌症是一种多因素疾病，需要确定新的治疗靶点。抑制Bcl-2以触发促凋亡信号被认为是癌症治疗的一种有前途的策略。在当前工作中，我们旨在设计和合成一系列新的苯并咪唑和吲哚衍生物，作为Bcl-2蛋白的抑制剂。市场上的全Bcl-2抑制剂obatoclax是采用结构修饰的主要框架化合物。将obatoclax的吡咯甲亚甲基连接物替换为直链烷胺或羧酰肼亚甲基连接物，提供了新的化合物。这种策略允许合成化合物的结构灵活性得到改善，采用有利的操作方式更好地适配Bcl-2的主要疏水口袋。通过MTT细胞毒性分析、细胞周期分析、RT-PCR、ELISA和DNA断裂进一步研究了合成化合物的抗癌活性。细胞毒性结果显示，化合物8a、8b和8c对MDA-MB-231/乳腺癌细胞表现出有希望的细胞毒性（IC50 = 12.69 ± 0.84至12.83 ± 3.50 µM），而8a和8c对A549/肺腺癌细胞显示出明显的活性（IC50 = 23.05 ± 1.45和11.63 ± 2.57 µM，分别）。通过分子对接确认了Bcl-2抑制途径，显示了显著的对接能量和与关键Bcl-2口袋残基的相互作用。此外，最活性的化合物8b通过RT-PCR分析显示了促凋亡/抗凋亡基因Bax、Bcl-2、caspase-3、-8和-9的显著上调表达水平。通过引入8b到热熔均质化技术制备的药物固体/脂质纳米粒子配方进行了化合物的药理学特性改进，并评估了包封效率、粒径和Zeta电位。化合物的细胞毒性活性得到了显著改善。总之，8b被引入为有前途的抗癌首选候选化合物，值得在未来的精细化首选优化和开发研究中进行探索，同时通过体内临床前研究探讨其潜力。

  DOI：

  10.3390/ph14020113

文献信息

• Design, synthesis, spectroscopic characterization, in vitro tyrosinase inhibition, antioxidant evaluation, in silico and kinetic studies of substituted indole-carbohydrazides
  作者：Aida Iraji、Negar Sheikhi、Mahshid Attarroshan、Gholam Reaz Sharifi Ardani、Maryam Kabiri、Ali Naghibi Bafghi、Farzad Kobarfard、Zahra Rezaei、Mehdi Khoshneviszadeh、Alireza Foroumadi、Seyedeh Sara Mirfazli

  DOI：10.1016/j.bioorg.2022.106140

  日期：2022.12

  analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC50 values in the range of 0.070 to > 100 μM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC50 = 0.070 μM), 8f (R = 4-OH, IC50 = 0.072 μM), and 19e (IC50 = 0.19 μM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited

  在目前的研究中，合理设计和合成了 25 种与不同芳基取代相连的吲哚-碳酰肼衍生物。所有衍生物的结构均使用不同的光谱技术进行了确认，包括1 H NMR、13 C NMR、质谱和元素分析。所有合成化合物的酪氨酸酶抑制活性均表现出 0.070 至 > 100 μM 范围内的 IC 50值。构效关系表明，化合物4f（R = 4-OH，IC 50  = 0.070 μM）、8f（R = 4-OH，IC 50  = 0.072 μM）和19e（IC 50  = 0.19 μM）对发现 R 位置的 -OH 取代基是所有三个测试系列中最活跃的成员。动力学研究表明，化合物4f、8f和19e是混合型抑制剂。此外，对最有效的衍生物进行了毒性和基于细胞的抗黑素生成评估，结果表明4f、8f和19e在 8 µM 时没有毒性，并且在 8 µM 时黑色素含量百分比降至 68.43、72.61、73.47 μM，分别。在计
• Vega, A. Monge; Palop, J. A.; Martinez, M. T., Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 249 - 256
  作者：Vega, A. Monge、Palop, J. A.、Martinez, M. T.、Alvarez, E. Fernandez

  DOI：——

  日期：——
• Design, synthesis and QSAR study of arylidene indoles as anti-platelet aggregation inhibitors
  作者：Seyedeh Sara Mirfazli、Mehdi Khoshneviszadeh、Mohammad Jeiroudi、Alireza Foroumadi、Farzad Kobarfard、Abbas Shafiee

  DOI：10.1007/s00044-015-1440-7

  日期：2016.1

  A series of novel substituted indole carbohydrazide was synthesized and evaluated for anti-platelet aggregation activity. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis and were evaluated for their ability to inhibit platelet aggregation induced by adenosine diphosphate, arachidonic acid (AA) and collagen. Compounds 3e and 3b exhibited the highest activities against the platelet aggregation induced by collagen with IC50 values of 12.7 and 13.3 mu M, respectively, and 2h with IC50 value of 51.88 mu M and 2i with IC50 of 44.38 mu M efficiently inhibited platelet aggregation induced by AA. The QSAR investigation indicated the importance of the topological, constitutional and geometrical parameters (PW3, PW4, LP1 and GATS6v) in describing the anti-platelet aggregation activity of the synthesized hydrazides. Evaluation of cytotoxic activity of the compounds against L929 cell line and three cancer cell lines revealed that none of the compounds have significant cytotoxicity.
• Salicylaldehyde-indole-2-acylhydrazone: a simple, colorimetric and absorption ratiometric chemosensor for acetate ion
  作者：Xiao-ping Bao、Peng-cheng Zheng、Yong Liu、Zan Tan、Yu-hui Zhou、Bao-an Song

  DOI：10.1080/10610278.2012.758368

  日期：2013.4.1

  A simple anion receptor (i.e. salicylaldehyde-indole-2-acylhydrazone) was synthesised and its recognition properties were investigated by naked-eye observation, UVvis titration spectra, 1H NMR spectroscopy and DFT calculations. The obtained results indicated that this receptor could realise the selective colorimetric sensing and absorption ratiometric response towards AcO in CH3CNDMSO medium, by virtue of threefold intermolecular hydrogen bonding interactions formed with phenolic OH, indole NH and amide NH.
• Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein
  作者：Manar I. Nagy、Khaled M. Darwish、Safaa M. Kishk、Mohamed A. Tantawy、Ali M. Nasr、Mona Qushawy、Shady A. Swidan、Samia M. Mostafa、Ismail Salama

  DOI：10.3390/ph14020113

  日期：——

  Cancer is a multifactorial disease necessitating identification of novel targets for its treatment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole- and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 µM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 µM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3, -8, and -9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.

  癌症是一种多因素疾病，需要确定新的治疗靶点。抑制Bcl-2以触发促凋亡信号被认为是癌症治疗的一种有前途的策略。在当前工作中，我们旨在设计和合成一系列新的苯并咪唑和吲哚衍生物，作为Bcl-2蛋白的抑制剂。市场上的全Bcl-2抑制剂obatoclax是采用结构修饰的主要框架化合物。将obatoclax的吡咯甲亚甲基连接物替换为直链烷胺或羧酰肼亚甲基连接物，提供了新的化合物。这种策略允许合成化合物的结构灵活性得到改善，采用有利的操作方式更好地适配Bcl-2的主要疏水口袋。通过MTT细胞毒性分析、细胞周期分析、RT-PCR、ELISA和DNA断裂进一步研究了合成化合物的抗癌活性。细胞毒性结果显示，化合物8a、8b和8c对MDA-MB-231/乳腺癌细胞表现出有希望的细胞毒性（IC50 = 12.69 ± 0.84至12.83 ± 3.50 µM），而8a和8c对A549/肺腺癌细胞显示出明显的活性（IC50 = 23.05 ± 1.45和11.63 ± 2.57 µM，分别）。通过分子对接确认了Bcl-2抑制途径，显示了显著的对接能量和与关键Bcl-2口袋残基的相互作用。此外，最活性的化合物8b通过RT-PCR分析显示了促凋亡/抗凋亡基因Bax、Bcl-2、caspase-3、-8和-9的显著上调表达水平。通过引入8b到热熔均质化技术制备的药物固体/脂质纳米粒子配方进行了化合物的药理学特性改进，并评估了包封效率、粒径和Zeta电位。化合物的细胞毒性活性得到了显著改善。总之，8b被引入为有前途的抗癌首选候选化合物，值得在未来的精细化首选优化和开发研究中进行探索，同时通过体内临床前研究探讨其潜力。