2-[(4-nitrobenzylidene)amino]-4,5,6,7-tetrahydro-4Hbenzo[b]thiophene-3-carbonitrile | 69438-10-4

• 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: 2-[(4-nitrobenzylidene)amino]-4,5,6,7-tetrahydro-4Hbenzo[b]thiophene-3-carbonitrile
• 英文别名: 2-[(4-nitrophenyl) amino]-4,5,6,7-tetrahydro-4H-benzo[β]thiophene-3-carbonitrile；6CN10；2-[(4-Nitrophenyl)methylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
• CAS: 69438-10-4
• 化学式: C₁₆H₁₃N₃O₂S
• mdl: MFCD00403572
• 分子量: 311.364
• InChiKey: GZTZMWJZAWZZQK-UHFFFAOYSA-N

物化性质

• 熔点：
  185-187 °C
• 沸点：
  588.0±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  环己酮 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 生成 2-[(4-nitrobenzylidene)amino]-4,5,6,7-tetrahydro-4Hbenzo[b]thiophene-3-carbonitrile
  参考文献：
  名称：

  2-Amino-thiophene derivatives present antileishmanial activity mediated by apoptosis and immunomodulation in vitro

  摘要：

  This study evaluated the effects of 2-amino-thiophene derivatives on the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and their possible mechanisms of action. Initially, we evaluated the antileishmanial activity of ten 2-amino-thiophene derivatives on promastigote and axenic amastigote forms of Leishmania amazonensis and their cytotoxicity against murine macrophages and human red blood cells. Three promising compounds were selected for studies of the cell death process using flow cytometry analysis and a DNA fragmentation assay. The effects of the compounds were assessed on intramacrophagic amastigotes, and the modulation of cytokine and NO production was investigated. All thiophene derivatives showed antileishmanial activity against promastigotes and axenic amastigotes with less toxicity for murine macrophages and human red blood cells. The best values were obtained for compounds containing a lateral indole ring. Docking studies suggested that these compounds played an important role in inhibiting trypanothione reductase (TryR) activity. The selected compounds SB-200, SB-44, and SB-83 induced apoptosis in promastigotes involving phosphatidylserine externalization and DNA fragmentation in a pattern similar to that observed for the positive control. Additionally, SB-200, SB-44, and SB-83 significantly reduced the infection index of macrophages by the parasites; for compounds SB-200 and SB-83 this reduction was associated with increased TNF-alpha, IL-12, and NO levels. This study demonstrated the effective and selective action of 2-amino-thiophene derivatives against L. amazonensis, resulting in apoptosis-like cell death and immunomodulation in vitro. The results suggest that they are promising compounds for the development of new leishmanicidal drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.011

文献信息

• 2-Amino-thiophene derivatives present antileishmanial activity mediated by apoptosis and immunomodulation in vitro
  作者：Klinger Antonio da Franca Rodrigues、Cínthia Nóbrega de Sousa Dias、Patrícia Lima do Nascimento Néris、Juliana da Câmara Rocha、Marcus Tullius Scotti、Luciana Scotti、Sandra Rodrigues Mascarenhas、Robson Cavalcante Veras、Isac Almeida de Medeiros、Tatjana de Souza Lima Keesen、Tiago Bento de Oliveira、Maria do Carmo Alves de Lima、Tatiane Luciano Balliano、Thiago Mendonça de Aquino、Ricardo Olímpio de Moura、Francisco Jaime Bezerra Mendonça Junior、Márcia Rosa de Oliveira

  DOI：10.1016/j.ejmech.2015.10.011

  日期：2015.12

  This study evaluated the effects of 2-amino-thiophene derivatives on the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and their possible mechanisms of action. Initially, we evaluated the antileishmanial activity of ten 2-amino-thiophene derivatives on promastigote and axenic amastigote forms of Leishmania amazonensis and their cytotoxicity against murine macrophages and human red blood cells. Three promising compounds were selected for studies of the cell death process using flow cytometry analysis and a DNA fragmentation assay. The effects of the compounds were assessed on intramacrophagic amastigotes, and the modulation of cytokine and NO production was investigated. All thiophene derivatives showed antileishmanial activity against promastigotes and axenic amastigotes with less toxicity for murine macrophages and human red blood cells. The best values were obtained for compounds containing a lateral indole ring. Docking studies suggested that these compounds played an important role in inhibiting trypanothione reductase (TryR) activity. The selected compounds SB-200, SB-44, and SB-83 induced apoptosis in promastigotes involving phosphatidylserine externalization and DNA fragmentation in a pattern similar to that observed for the positive control. Additionally, SB-200, SB-44, and SB-83 significantly reduced the infection index of macrophages by the parasites; for compounds SB-200 and SB-83 this reduction was associated with increased TNF-alpha, IL-12, and NO levels. This study demonstrated the effective and selective action of 2-amino-thiophene derivatives against L. amazonensis, resulting in apoptosis-like cell death and immunomodulation in vitro. The results suggest that they are promising compounds for the development of new leishmanicidal drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.