9,9'-(1,2-ethanedioxybisdimethylenediamino)diacridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9,9'-(1,2-ethanedioxybisdimethylenediamino)diacridine
• 英文别名: N,N'-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(acridin-9-amine)；N,N-bis(9-acridinyl)-1,8-diamino-3,6-dioxaoctane；N-[2-[2-[2-(acridin-9-ylamino)ethoxy]ethoxy]ethyl]acridin-9-amine
• 化学式: C₃₂H₃₀N₄O₂
• 分子量: 502.616
• InChiKey: SNXPMEFRDBMDTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  68.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苯基邻氨基苯甲酸 在 硫酸 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 13.0h， 生成 9,9'-(1,2-ethanedioxybisdimethylenediamino)diacridine
  参考文献：
  名称：

  Syntheses and Evaluation of New Bisacridine Derivatives for Dual Binding of G-Quadruplex and i-Motif in Regulating Oncogene c-myc Expression

  摘要：

  The c-myc oncogene is an important regulator for cell growth and differentiation, and its aberrant overexpression is closely related to the occurrence and development of various cancers. Thus, the suppression of c-myc transcription and expression has been investigated for cancer treatment. In this study, various new bisacridine derivatives were synthesized and evaluated for their binding with c-myc promoter G-quadruplex and i-motif. We found that a9 could bind to and stabilize both G-quadruplex and i-motif, resulting in the downregulation of c-myc gene transcription. a9 could inhibit cancer cell proliferation and induce SiHa cell apoptosis and cycle arrest. a9 exhibited tumor growth inhibition activity in a SiHa xenograft tumor model, which might be related to its binding with c-myc promoter G-quadruplex and i-motif. Our results suggested that a9 as a dual G-quadruplex/i-motif binder could be effective in both oncogene replication and transcription and become a promising lead compound for further development with improved potency and selectivity.

  DOI：

  10.1021/acs.jmedchem.9b01917

文献信息

• Synthesis of Monomeric and Dimeric Acridine Compounds as Potential Therapeutics in Alzheimer and Prion Diseases
  作者：René Csuk、Alexander Barthel、Christian Raschke、Ralph Kluge、Dieter Ströhl、Lothar Trieschmann、Gerald Böhm

  DOI：10.1002/ardp.200900065

  日期：2009.12

  spacered dimeric acridine compounds was prepared. Their ability to interrupt the protein association of prion‐ and Alzheimer‐specific proteins and Ab peptides was explored using a fast screening system based on FACS analysis. The bis‐acridines displayed a higher activity than the corresponding monomers. Among these derivatives, best results were obtained with the 2,4‐dimethoxy‐6‐nitro compound 7h for

  从取代的 9-氯吖啶开始，制备了一系列奎纳克林和间隔二聚吖啶化合物。使用基于 FACS 分析的快速筛选系统探索了它们中断朊病毒和阿尔茨海默特异蛋白与 Ab 肽的蛋白质结合的能力。双吖啶比相应的单体表现出更高的活性。在这些衍生物中，Aβ-肽的 2,4-二甲氧基-6-硝基化合物 7h 和 PrP 的 2-甲氧基-6-硝基化合物 7f 获得了最好的结果。
• Acheson, R. Morrin; Constable, Edwin C.; Wright, R. Gordon McR., Journal of Chemical Research, Miniprint, 1983, # 1, p. 101 - 132
  作者：Acheson, R. Morrin、Constable, Edwin C.、Wright, R. Gordon McR.、Taylor, Grahame M.

  DOI：——

  日期：——
• ACHSON, R. M.;CONSTABLE, E. C.;WRIGHT, R. G. ,, MCR.;TAYLOR, G. N., J. CHEM. RES. MICROFICHE, 1983, N 1, 2-3
  作者：ACHSON, R. M.、CONSTABLE, E. C.、WRIGHT, R. G. ,, MCR.、TAYLOR, G. N.

  DOI：——

  日期：——
• Syntheses and Evaluation of New Bisacridine Derivatives for Dual Binding of G-Quadruplex and i-Motif in Regulating Oncogene <i>c-myc</i> Expression
  作者：Guotao Kuang、Meiling Zhang、Shuangshuang Kang、Dexuan Hu、Xiaoya Li、Zuzhuang Wei、Xue Gong、Lin-Kun An、Zhi-Shu Huang、Bing Shu、Ding Li

  DOI：10.1021/acs.jmedchem.9b01917

  日期：2020.9.10

  The c-myc oncogene is an important regulator for cell growth and differentiation, and its aberrant overexpression is closely related to the occurrence and development of various cancers. Thus, the suppression of c-myc transcription and expression has been investigated for cancer treatment. In this study, various new bisacridine derivatives were synthesized and evaluated for their binding with c-myc promoter G-quadruplex and i-motif. We found that a9 could bind to and stabilize both G-quadruplex and i-motif, resulting in the downregulation of c-myc gene transcription. a9 could inhibit cancer cell proliferation and induce SiHa cell apoptosis and cycle arrest. a9 exhibited tumor growth inhibition activity in a SiHa xenograft tumor model, which might be related to its binding with c-myc promoter G-quadruplex and i-motif. Our results suggested that a9 as a dual G-quadruplex/i-motif binder could be effective in both oncogene replication and transcription and become a promising lead compound for further development with improved potency and selectivity.