N1,N1'-(ethane-1,2-diyl)bis(N3-(2,7-dimethylacridin-9-yl)propane-1,3-diamine)

• 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,N1'-(ethane-1,2-diyl)bis(N3-(2,7-dimethylacridin-9-yl)propane-1,3-diamine)
• 英文别名: N'-(2,7-dimethylacridin-9-yl)-N-[2-[3-[(2,7-dimethylacridin-9-yl)amino]propylamino]ethyl]propane-1,3-diamine
• 化学式: C₃₈H₄₄N₆
• 分子量: 584.808
• InChiKey: BCKVBXNVGAXDQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  73.9
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,7-dimethylacridin-9(10H)-one 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 11.0h， 生成 N1,N1'-(ethane-1,2-diyl)bis(N3-(2,7-dimethylacridin-9-yl)propane-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

• 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.