3,4-dihydro-6,6-dimethyl-6H-2-(3-indolyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 3,4-dihydro-6,6-dimethyl-6H-2-(3-indolyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole
• 英文别名: 4,5-dihydro-6,6-dimethyl-6H-2-(3^,-indolyl)-pyran[b-4,3]naphth[1,2-d]imidazole；2-(1H-Indol-3-yl)-6,6-dimethyl-3,4,5,6-tetrahydrobenzo[7,8]chromeno[5,6-d]imidazole；4-(1H-indol-3-yl)-10,10-dimethyl-11-oxa-3,5-diazatetracyclo[11.4.0.02,6.07,12]heptadeca-1(17),2(6),4,7(12),13,15-hexaene
• 化学式: C₂₄H₂₁N₃O
• 分子量: 367.45
• InChiKey: QLADCCGURIKZSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  53.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  黄钟花醌 在 硫酸 、 ammonium acetate 、 溶剂黄146 作用下， 生成 3,4-dihydro-6,6-dimethyl-6H-2-(3-indolyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole
  参考文献：
  名称：

  Novel N,N-di-alkylnaphthoimidazolium derivative of β-lapachone impaired Trypanosoma cruzi mitochondrial electron transport system

  摘要：

  DOI：

  10.1016/j.biopha.2020.111186

文献信息

• Rhodium(III)-Catalyzed C–H/N–H Alkyne Annulation of Nonsymmetric 2-Aryl (Benz)imidazole Derivatives: Photophysical and Mechanistic Insights
  作者：Gleiston G. Dias、Esther R. S. Paz、Juliana Y. Kadooca、Adão A. Sabino、Luiz A. Cury、Kohei Torikai、Carlos A. de Simone、Felipe Fantuzzi、Eufrânio N. da Silva Júnior

  DOI：10.1021/acs.joc.0c02054

  日期：2021.1.1

  enabled C–H/N–H alkyne annulation of nonsymmetric imidazole derivatives. This study encompasses the synthesis of imidazoles from a naturally occurring quinoidal compound and their use for the preparation of rigid π-extended imidazole derivatives with outstanding fluorescence. Our study also brings to light the photophysical aspects and the mechanism of the reaction studied via computational calculations

  铑（III）催化可实现非对称咪唑衍生物的C–H / N–H炔烃环化。这项研究涵盖了由天然存在的醌型化合物合成咪唑及其在制备具有出色荧光性的刚性π-延伸咪唑衍生物中的用途。我们的研究还揭示了光物理方面以及通过计算计算研究的反应机理。该方法为合成具有多种化学和生物学应用的荧光化合物提供了一种有效且通用的工具。
• Mitochondrial disfunction and ROS production are essential for anti-Trypanosoma cruzi activity of β-lapachone-derived naphthoimidazoles
  作者：Ana Cristina S. Bombaça、Paula G. Viana、Augusto C.C. Santos、Thaissa L. Silva、Aline Beatriz M. Rodrigues、Ana Carolina R. Guimarães、Marilia O.F. Goulart、Eufrânio N. da Silva Júnior、Rubem F.S. Menna-Barreto

  DOI：10.1016/j.freeradbiomed.2018.11.012

  日期：2019.1

  Chagas disease is caused by the hemoflagellate protozoa Trypanosoma cruzi and is one of the most important neglected tropical diseases, especially in Latin American countries, where there is an association between low-income populations and mortality. The nitroderivatives used in current chemotherapy are far from ideal and present severe limitations, justifying the continuous search for alternative drugs. Since the 1990s, our group has been investigating the trypanocidal activity of natural naphthoquinones and their derivatives, and three naphthoimidazoles (N1, N2 and N3) derived from beta-lapachone were found to be most effective in vitro. Analysis of their mechanism of action via cellular, molecular and proteomic approaches indicates that the parasite mitochondrion contains one of the primary targets of these compounds, trypanothione synthetase (involved in trypanothione production), which is overexpressed after treatment with these compounds. Here, we further evaluated the participation of the mitochondria and reactive oxygen species (ROS) in the anti-T. cruzi action of naphthoimidazoles. Preincubation of epimastigotes and trypomastigotes with antioxidants (alpha-tocopherol and urate) strongly protected the parasites from the trypanocidal effect of naphthoimidazoles, decreasing the ROS levels produced and reverting the mitochondrial swelling phenotype. The addition of pro-oxidants (menadione and H2O2) before the treatment induced an increase in parasite lysis. Despite the O-2 uptake and mitochondrial complex activity being strongly reduced by N1, N2 and N3, urate partially restored the mitochondrial metabolism only in N1-treated parasites. In parallel, MitoTEMPO, a mitochondrial-targeted antioxidant, protected the functionality of the mitochondria in N2- and N3-treated parasites. In addition, the trypanothione reductase activity was remarkably increased after treatment with N1 and N3, and molecular docking demonstrated that these two compounds were positioned in pockets of this enzyme. Based on our findings, the direct impairment of the mitochondrial electron transport chain by N2 and N3 led to an oxidative misbalance, which exacerbated ROS generation and led to parasite death. Although other mechanisms cannot be discounted, mainly in N1-treated parasites, further investigations are required.
• Pinto; Dantas; De Moura, Arzneimittel-Forschung/Drug Research, 2000, vol. 50, # 12, p. 1120 - 1128
  作者：Pinto、Dantas、De Moura、Emery、Polequevitch、Pinto、De Castro、Pinto

  DOI：——

  日期：——
• Novel N,N-di-alkylnaphthoimidazolium derivative of β-lapachone impaired Trypanosoma cruzi mitochondrial electron transport system
  作者：Ana Cristina S. Bombaça、Leonardo A. Silva、Otávio Augusto Chaves、Lorrainy S. da Silva、Juliana M.C. Barbosa、Ari M. da Silva、Aurélio B.B. Ferreira、Rubem F.S. Menna-Barreto

  DOI：10.1016/j.biopha.2020.111186

  日期：2021.3