N’-((5-nitrofuran-2-yl)methylene)benzohydrazide | 28123-74-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N’-((5-nitrofuran-2-yl)methylene)benzohydrazide
• 英文别名: N′-(5-nitrofuran-2-ylmethylene)benzohydrazide；N'-((5-nitrofuran-2-yl)methylene)benzohydrazide；N-((5-nitrofuran-2-yl)methylene)benzohydrazide；5-nitrofurfurylidene benzoylhydrazone；N'-(5-nitrofurfurylidene)benzhydrazide；N-[(5-nitrofuran-2-yl)methylideneamino]benzamide
• CAS: 28123-74-2
• 化学式: C₁₂H₉N₃O₄
• mdl: MFCD00607356
• 分子量: 259.221
• InChiKey: VFOAAIIORKZVIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  zinc(II) chloride 、 N’-((5-nitrofuran-2-yl)methylene)benzohydrazide 以 甲醇 为溶剂， 生成 Zn(5-nitrofurfurylidenebenzoylhydrazone)2
  参考文献：
  名称：

  Rao, Surya D.; Ganorkar, M. C., Journal of the Indian Chemical Society, 1981, vol. 58, p. 217 - 219

  摘要：

  DOI：
• 作为产物：
  描述：

  苯甲酸 在 硫酸 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成 N’-((5-nitrofuran-2-yl)methylene)benzohydrazide
  参考文献：
  名称：

  N-酰腙和新型1,3,4-恶二唑衍生物的合成、分子性质预测和抗葡萄球菌活性。

  摘要：

  通过N环化合成了五种新的1-(2-(5-硝基呋喃-2-基)-5-(芳基)-1,3,4-恶二唑-3-(2H)-基)乙酮化合物5a-e -酰腙4a-e与乙酸酐在回流条件下反应。它们的结构通过IR、1H-NMR和13C-NMR进行了充分表征。此外，1,3,4-恶二唑 5a-e 和 N-酰基腙 4a-e 的抗菌活性评估显示，对多种金黄色葡萄球菌菌株具有很强的活性，MIC 介于 4 μg/mL 至 32 μg/mL 之间。对 Lipinski 五法则参数以及拓扑极性表面积 (TPSA)、吸收百分比 (% ABS)、药物相似性和药物评分的计算机研究表明，这些化合物，特别是 4a 和 5d，有潜力成为新候选药物。

  DOI：

  10.3390/molecules17055095

文献信息

• Nitrofuran drugs beyond redox cycling: Evidence of Nitroreduction-independent cytotoxicity mechanism
  作者：C. Gallardo-Garrido、Y. Cho、J. Cortés-Rios、D. Vasquez、C.D. Pessoa-Mahana、R. Araya-Maturana、H. Pessoa-Mahana、M. Faundez

  DOI：10.1016/j.taap.2020.115104

  日期：2020.8

  ROS exhibited the highest cell toxicity among all derivatives. Inhibition of cytosolic glutathione-S-transferase activity by some derivatives was also observed. Finally, only nitrofuran derivatives displayed antibacterial effect. Results suggest that the combined 2-hydrazonylfuran moiety, redox cycling of 5-nitrofuran, and inhibitory effects on antioxidant enzymes, would be finally responsible for the

  硝基呋喃（5-硝基-2-肼基呋喃为药效团）是一组广泛使用的抗菌药物，但同时也具有多种副作用。硝基呋喃类药物的细胞毒性作用的分子机制尚未清楚地了解。宿主酶使5-硝基基团单电子还原和通过氧化还原循环产生ROS被认为是细胞毒性的机制。但是，目前的证据表明，硝基呋喃ROS的产生本身不能解释与硝基呋喃消耗有关的全部毒性作用，从而提出了与硝基还原无关的毒性机制。 在目前的工作中，一系列的硝基呋喃药物硝化和非硝化衍生物的合成和评价在体外对它们的细胞毒性，ROS -产生容量，效果上GSH-小号转移酶和抗菌活性。 我们的研究表明，在人类细胞中，未硝化的衍生物的毒性低于母体药物，但尽管未进入氧化还原循环机制，但仍意外地保留了产生与硝基呋喃类似量的细胞内ROS的能力。此外，一些未硝化的衍生物尽管不能产生ROS，但在所有衍生物中表现出最高的细胞毒性。还观察到一些衍生物抑制了胞质谷胱甘肽-S-转移酶的活性。最后，仅硝基呋喃衍生物显示出抗菌作用。
• Analogs of nitrofuran antibiotics are potent GroEL/ES inhibitor pro-drugs
  作者：Mckayla Stevens、Chris Howe、Anne-Marie Ray、Alex Washburn、Siddhi Chitre、Jared Sivinski、Yangshin Park、Quyen Q. Hoang、Eli Chapman、Steven M. Johnson

  DOI：10.1016/j.bmc.2020.115710

  日期：2020.11

  intestine cells in vitro. Initially, only the hydroxyquinoline-bearing analogs were found to be potent inhibitors in our GroEL/ES-mediated substrate refolding assays; however, subsequent testing in the presence of an E. coli nitroreductase (NfsB) in situ indicated that metabolites of the nitrofuran-bearing analogs were potent GroEL/ES inhibitor pro-drugs. Consequently, this study has identified a new target

  在之前的两项研究中，我们将化合物1鉴定为中度 GroEL/ES 抑制剂，对革兰氏阳性菌和革兰氏阴性菌具有弱至中度抗菌活性，包括枯草芽孢杆菌、耐甲氧西林金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌和 SM101埃希氏菌大肠杆菌（其脂多糖生物合成途径受损，使细菌对药物更具渗透性）。从这些研究中延伸，我们开发了两个系列与主要子结构类似于那些已知抗菌剂，nitroxoline（羟基喹啉结构部分）和nifuroxazide /呋喃妥因（类似物的双-cyclic- Ñ-酰基腙支架）。通过生化和基于细胞的检测，我们确定了有效的 GroEL/ES 抑制剂，可选择性地阻断粪肠球菌、金黄色葡萄球菌和大肠杆菌的增殖，并且对体外人结肠和肠道细胞的细胞毒性较低。最初，在我们的 GroEL/ES 介导的底物重折叠试验中，只有含羟基喹啉的类似物被发现是有效的抑制剂；然而，随后在存在大肠杆菌硝基还原酶 (NfsB) 的情况
• Synthesis, Molecular Properties Prediction, and Anti-staphylococcal Activity of N-Acylhydrazones and New 1,3,4-Oxadiazole Derivatives
  作者：Cledualdo Soares de Oliveira、Bruno Freitas Lira、Vivyanne dos Santos Falcão-Silva、Jose Pinto Siqueira-Junior、Jose Maria Barbosa-Filho、Petronio Filgueiras de Athayde-Filho

  DOI：10.3390/molecules17055095

  日期：——

  acetic anhydride under reflux conditions. Their structures were fully characterized by IR, ¹H-NMR, and ¹³C-NMR. Furthermore, evaluations of the antibacterial activity of the 1,3,4-oxadiazoles 5a-e and N-acylhydrazones 4a-e showed strong activity against several strains of Staphylococcus aureus, with MICs between 4 μg/mL to 32 μg/mL. In silico studies of the parameters of Lipinski's Rule of Five, as well

  通过N环化合成了五种新的1-(2-(5-硝基呋喃-2-基)-5-(芳基)-1,3,4-恶二唑-3-(2H)-基)乙酮化合物5a-e -酰腙4a-e与乙酸酐在回流条件下反应。它们的结构通过IR、1H-NMR和13C-NMR进行了充分表征。此外，1,3,4-恶二唑 5a-e 和 N-酰基腙 4a-e 的抗菌活性评估显示，对多种金黄色葡萄球菌菌株具有很强的活性，MIC 介于 4 μg/mL 至 32 μg/mL 之间。对 Lipinski 五法则参数以及拓扑极性表面积 (TPSA)、吸收百分比 (% ABS)、药物相似性和药物评分的计算机研究表明，这些化合物，特别是 4a 和 5d，有潜力成为新候选药物。
• 5-Nitro-2-furfuriliden derivatives as potential anti-Trypanosoma cruzi agents: Design, synthesis, bioactivity evaluation, cytotoxicity and exploratory data analysis
  作者：Fanny Palace-Berl、Salomão Dória Jorge、Kerly Fernanda Mesquita Pasqualoto、Adilson Kleber Ferreira、Durvanei Augusto Maria、Rodrigo Rocha Zorzi、Leandro de Sá Bortolozzo、José Ângelo Lauletta Lindoso、Leoberto Costa Tavares

  DOI：10.1016/j.bmc.2013.06.017

  日期：2013.9

  The anti-Trypanosoma cruzi activity of 5-nitro-2-furfuriliden derivatives as well as the cytotoxicity of these compounds on J774 macrophages cell line and FN1 human fibroblast cells were investigated in this study. The most active compounds of series I and II were 4-butyl-[N'-(5-nitrofuran-2-y1) methylene] benzidrazide (3g; IC50= 1.05 mu M +/- 0.07) and 3-acety1-5-(4-butylpheny1)-2-(5-nitrofuran-2-y1)-2,3-dihydro,1,3,4-oxadiazole (4g; IC50 = 8.27 mu M +/- 0.42), respectively. Also, compound 3g was more active than the standard drugs, benznidazole (IC50= 22.69 u mu M 1.96) and nifurtimox (IC50= 3.78 mu M +/- 0.10). Regarding the cytotoxicity assay, the 3g compound presented IC50 value of 28.05 mu M (SI = 26.71) against J774 cells. For the FN1 fibroblast assay, 3g showed IC50 value of 98 mu M (SI = 93.33). On the other hand, compound 4g presented a cytotoxicity value on J774 cells higher than 400 mu M (SI >48), and for the FN1 cells its IC50 value was 186 mu M (SI = 22.49). Moreover, an exploratory data analysis, which comprises hierarchical cluster (HCA) and principal component analysis (PCA), was carried out and the findings were complementary. The molecular properties that most influenced the compounds' grouping were ClogP and total dipole moment, pointing out the need of a lipophilic/hydrophilic balance in the designing of novel potential anti-T. cruzi molecules. (C) 2013 Elsevier Ltd. All rights reserved.
• Exploring 5-nitrofuran derivatives against nosocomial pathogens: Synthesis, antimicrobial activity and chemometric analysis
  作者：Rodrigo Rocha Zorzi、Salomão Dória Jorge、Fanny Palace-Berl、Kerly Fernanda Mesquita Pasqualoto、Leandro de Sá Bortolozzo、André Murillo de Castro Siqueira、Leoberto Costa Tavares

  DOI：10.1016/j.bmc.2014.03.044

  日期：2014.5

  The burden of nosocomial or health care-associated infection (HCAI) is increasing worldwide. According to the World Health Organization (WHO), it is several fold higher in low-and middle-income countries. Considering the multidrug-resistant infections, the development of new and more effective drugs is crucial. Herein, two series (I and II) of 5-nitrofuran derivatives were designed, synthesized and assayed against microorganisms, including Gram-positive and -negative bacteria, and fungi. The pathogens screened was directly related to either the most currently relevant HCAI, or to multidrug-resistant infection caused by MRSA/VRSA strains, for instance. The sets I and II were composed by substituted[ N'-(5-nitrofuran-2-yl)methylene]benzhydrazide and 3-acetyl-5-(substituted-phenyl)-2-(5-nitro-furan-2-yl)-2,3-dihydro-1,3,4-oxadiazole compounds, respectively. The selection of the substituent groups was based upon physicochemical properties, such as hydrophobicity and electronic effect. The compounds have showed better activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. The findings from S. aureus strain, which was more susceptible, were used to investigate the intersamples and intervariables relationships by applying chemometric methods. It is noteworthy that the compound 4-butyl-[N'-(5-nitrofuran-2-yl) methylene] benzhydrazide has showed similar MIC value to vancomycin, which is the reference drug for multidrug-resistant S. aureus infections. Taken the findings together, the 5-nitrofuran derivatives might be indeed considered as promising hits to develop novel antimicrobial drugs to fight against nosocomial infection. (C) 2014 Elsevier Ltd. All rights reserved.