5-nitro-1H-indole-2,3-dione-3-(4-butylthiosemicarbazone)

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-nitro-1H-indole-2,3-dione-3-(4-butylthiosemicarbazone)
• 化学式: C₁₃H₁₅N₅O₃S
• 分子量: 321.36
• InChiKey: MWJLBJXIZUKHIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.52
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108.66
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  吗啉 、 聚合甲醛 、 5-nitro-1H-indole-2,3-dione-3-(4-butylthiosemicarbazone) 以 乙醇 为溶剂， 反应 4.0h， 以79%的产率得到1-morpholinomethyl-5-nitro-1H-indole-2,3-dione-3-(4-butylthiosemicarbazone)
  参考文献：
  名称：

  Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives

  摘要：

  A new series of 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (3a-k) obtained by condensation of 5-nitro-1H-indole-2,3dione (1) with N-substituted-thiosemicarbazides (2a-k) were treated with morpholine or piperidine and formaldehyde to yield 1-morpholino/piperidinomethyl-5-nitroindole-2 3-dione-3-thiosemicarbazones (4a-m). The structures of all the compounds were determined by analytical and spectral (IR, H-1-NMR, EIMS) methods. Compounds 3b, 3c, 3f, 3k, 4a, 4c, 4f and 4l chosen as prototypes were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. All the compounds that passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Sulphorhodamine B (SRB) protein assay was used to estimate cell stability or growth. The most active compound was found to be 1-morpholinomethyl-5-nitroindole-2,3-dione-3-N(chlorophenyl)thiosemicarbazone (4l). This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumour cell line in vitro screen on a non-small cell lung cancer cell line (HOP-62, logo GI(50) value < -8.00) and on leukaemia cell lines (HL-60(TB), log(10) GI(50) value -6.30; MOLT-4, log(10) GI(50) value -6.18). (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(02)01416-2
• 作为产物：
  描述：

  5-硝基靛红 、 4-丁基-3-氨基硫脲 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以89%的产率得到5-nitro-1H-indole-2,3-dione-3-(4-butylthiosemicarbazone)
  参考文献：
  名称：

  Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives

  摘要：

  A new series of 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (3a-k) obtained by condensation of 5-nitro-1H-indole-2,3dione (1) with N-substituted-thiosemicarbazides (2a-k) were treated with morpholine or piperidine and formaldehyde to yield 1-morpholino/piperidinomethyl-5-nitroindole-2 3-dione-3-thiosemicarbazones (4a-m). The structures of all the compounds were determined by analytical and spectral (IR, H-1-NMR, EIMS) methods. Compounds 3b, 3c, 3f, 3k, 4a, 4c, 4f and 4l chosen as prototypes were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. All the compounds that passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Sulphorhodamine B (SRB) protein assay was used to estimate cell stability or growth. The most active compound was found to be 1-morpholinomethyl-5-nitroindole-2,3-dione-3-N(chlorophenyl)thiosemicarbazone (4l). This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumour cell line in vitro screen on a non-small cell lung cancer cell line (HOP-62, logo GI(50) value < -8.00) and on leukaemia cell lines (HL-60(TB), log(10) GI(50) value -6.30; MOLT-4, log(10) GI(50) value -6.18). (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(02)01416-2

文献信息

• Phenotypic and <i>in silico</i> studies for a series of synthetic thiosemicarbazones as New Delhi metallo-beta-lactamase carbapenemase inhibitors
  作者：Jonatham Souza Moreira、Danilo Santana Galvão、Carolina Ferreira Cavalcanti Xavier、Silvio Cunha、Samuel Silva da Rocha Pita、Joice Neves Reis、Humberto Fonseca de Freitas

  DOI：10.1080/07391102.2021.2001379

  日期：2022.12.26

  Inhibitory Concentration (FIC) ≤ 250 µM in the presence of meropenem (4 µg/mL). The most promising compound (FIC= 31.25 µM) also presented synergistic effect (FICI = 0.34). Docking and molecular dynamics studies on NDM-thiosemicarbazone complex suggested that 2,3-dihydro-1H-indol-2-one subunit interacts with catalytic zinc and interacted through hydrogen bonds with Asp124 acting like a carboxylic acid bioisostere

  摘要 过去二十年的特点是细菌对 β-内酰胺类药物产生耐药性，而碳青霉烯类衍生物是对抗多重耐药细菌的最终治疗方法。β-内酰胺酶表达与耐药性有关，这需要开发细菌耐药性阻断剂。丝氨酸-β-内酰胺酶和 β-内酰胺的药物抑制剂组合已成功用于治疗，尽管它们对新德里金属-β-内酰胺酶 (NDM) 没有活性。到目前为止，很少有化合物对产生 NDM 的细菌具有活性，也没有可用的特异性抑制剂。NDM抑制剂开发的合理策略从体外开始旨在寻找可以与 β-内酰胺抗生素协同作用的化合物的分析。因此，合成了八种缩氨基硫脲衍生物，并研究了它们逆转阴沟肠杆菌NDM 耐药表型的能力。 表型筛选表明，在美罗培南 (4 µg/mL) 存在的情况下，四种靛红-β-氨基硫脲显示分数抑制浓度 (FIC) ≤ 250 µM。最有前途的化合物 (FIC = 31.25 µM) 也呈现协同效应 (FICI = 0.34)。NDM-缩氨基硫脲络合物的对接和分子动力学研究表明，2
• Synthesis and structure–antituberculosis activity relationship of 1H-indole-2,3-dione derivatives
  作者：Nilgün Karalı、Aysel Gürsoy、Fatma Kandemirli、Nathaly Shvets、F. Betül Kaynak、Süheyla Özbey、Vasyl Kovalishyn、Anatholy Dimoglo

  DOI：10.1016/j.bmc.2007.05.063

  日期：2007.9.1

  New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-l-morpholino/piperidinomethyl-1Hindole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-IH-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3dione-3-thiosemicarbazones 4a-1, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives
  作者：Nilgün Karalı

  DOI：10.1016/s0223-5234(02)01416-2

  日期：2002.11

  A new series of 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (3a-k) obtained by condensation of 5-nitro-1H-indole-2,3dione (1) with N-substituted-thiosemicarbazides (2a-k) were treated with morpholine or piperidine and formaldehyde to yield 1-morpholino/piperidinomethyl-5-nitroindole-2 3-dione-3-thiosemicarbazones (4a-m). The structures of all the compounds were determined by analytical and spectral (IR, H-1-NMR, EIMS) methods. Compounds 3b, 3c, 3f, 3k, 4a, 4c, 4f and 4l chosen as prototypes were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. All the compounds that passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Sulphorhodamine B (SRB) protein assay was used to estimate cell stability or growth. The most active compound was found to be 1-morpholinomethyl-5-nitroindole-2,3-dione-3-N(chlorophenyl)thiosemicarbazone (4l). This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumour cell line in vitro screen on a non-small cell lung cancer cell line (HOP-62, logo GI(50) value < -8.00) and on leukaemia cell lines (HL-60(TB), log(10) GI(50) value -6.30; MOLT-4, log(10) GI(50) value -6.18). (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.