N1-(acridin-9-yl)-N3-(3-(acridin-9-ylamino)propyl)-N3-methylpropane-1,3-diamine | 97614-78-3

• 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: N1-(acridin-9-yl)-N3-(3-(acridin-9-ylamino)propyl)-N3-methylpropane-1,3-diamine
• 英文别名: N-acridin-9-yl-N'-[3-(acridin-9-ylamino)propyl]-N'-methylpropane-1,3-diamine
• CAS: 97614-78-3
• 化学式: C₃₃H₃₃N₅
• 分子量: 499.659
• InChiKey: YRQLDWJNQWMQLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  5

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 N1-(acridin-9-yl)-N3-(3-(acridin-9-ylamino)propyl)-N3-methylpropane-1,3-diamine
  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

• Potential antitumor agents. 44. Synthesis and antitumor activity of new classes of diacridines: importance of linker chain rigidity for DNA binding kinetics and biological activity
  作者：William A. Denny、Graham J. Atwell、Bruce C. Baguley、Laurence P. G. Wakelin

  DOI：10.1021/jm00149a005

  日期：1985.11

  Four classes of diacridines, joined at the 9-position by linker chains of varying length, rigidity, and polarity, were evaluated for DNA-binding properties and antitumor activity. Diacridines linked by flexible chains of varying polarity show relatively fast chromophore exchange kinetics among DNA binding sites but slower dissociation rates, suggesting the potential for considerable "creeping" of the drug along the helix, and are inactive in vivo. The exchange kinetics can be slowed dramatically by inclusion of positive charges in the side chain, but the resulting polycationic drugs are inactive in vivo, possibly due to poor distribution. Diacridines linked by a rigid, polar but neutral dicarbamoylpyrazole chain retain slow exchange kinetics, have a greatly reduced potential "creep rate", and possess good in vitro potency and significant in vivo antileukemic activity.
• 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.