2-[4-[2-[13-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1,9-diazatetracyclo[7.7.1.02,7.010,15]heptadeca-2(7),3,5,10(15),11,13-hexaen-5-yl]-3H-benzimidazol-5-yl]piperazin-1-yl]ethanol | 1395918-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-[2-[13-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1,9-diazatetracyclo[7.7.1.02,7.010,15]heptadeca-2(7),3,5,10(15),11,13-hexaen-5-yl]-3H-benzimidazol-5-yl]piperazin-1-yl]ethanol
• CAS: 1395918-70-3；1395918-71-4；1395918-72-5
• 化学式: C₄₁H₄₆N₁₀O₂
• 分子量: 710.882
• InChiKey: HTNUQAVTAPNVEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  53
• 可旋转键数：
  8
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (+/-)-2,8-bis(hydroxymethyl)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine 在 sodium metabisulfite 、 silica gel 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 2-[4-[2-[13-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1,9-diazatetracyclo[7.7.1.02,7.010,15]heptadeca-2(7),3,5,10(15),11,13-hexaen-5-yl]-3H-benzimidazol-5-yl]piperazin-1-yl]ethanol
  参考文献：
  名称：

  Stabilization and Structural Alteration of the G-Quadruplex DNA Made from the Human Telomeric Repeat Mediated by Tröger’s Base Based Novel Benzimidazole Derivatives

  摘要：

  Ligand-induced stabilization of the G-quadruplex DNA structure derived from the single-stranded 3'-overhang of the telomeric DNA is an attractive strategy for the inhibition of the telomerase activity. The agents that can induce/stabilize a DNA sequence into a G-quadruplex structure are therefore potential anticancer drugs. Herein we present the first report of the interactions of two novel bisbenzimidazoles (TBBz1 and TBBz2) based on Troger's base skeleton with the G-quadruplex DNA (G4DNA). These Troger's base molecules stabilize the G4DNA derived from a human telomeric sequence. Evidence of their strong interaction with the G4DNA has been obtained from CD spectroscopy, thermal denaturation, and UV-vis titration studies. These ligands also possess significantly higher affinity toward the G4DNA over the duplex DNA. The above results obtained are in excellent agreement with the biological activity, measured in vitro using a modified TRAP assay. Furthermore, the ligands are selectively more cytotoxic toward the cancerous cells than the corresponding noncancerous cells. Computational studies suggested that the adaptive scaffold might allow these ligands to occupy not only the G-quartet planes but also the grooves of the G4DNA.

  DOI：

  10.1021/jm300442r

文献信息

• Stabilization and Structural Alteration of the G-Quadruplex DNA Made from the Human Telomeric Repeat Mediated by Tröger’s Base Based Novel Benzimidazole Derivatives
  作者：Ananya Paul、Basudeb Maji、Santosh K. Misra、Akash K. Jain、K. Muniyappa、Santanu Bhattacharya

  DOI：10.1021/jm300442r

  日期：2012.9.13

  Ligand-induced stabilization of the G-quadruplex DNA structure derived from the single-stranded 3'-overhang of the telomeric DNA is an attractive strategy for the inhibition of the telomerase activity. The agents that can induce/stabilize a DNA sequence into a G-quadruplex structure are therefore potential anticancer drugs. Herein we present the first report of the interactions of two novel bisbenzimidazoles (TBBz1 and TBBz2) based on Troger's base skeleton with the G-quadruplex DNA (G4DNA). These Troger's base molecules stabilize the G4DNA derived from a human telomeric sequence. Evidence of their strong interaction with the G4DNA has been obtained from CD spectroscopy, thermal denaturation, and UV-vis titration studies. These ligands also possess significantly higher affinity toward the G4DNA over the duplex DNA. The above results obtained are in excellent agreement with the biological activity, measured in vitro using a modified TRAP assay. Furthermore, the ligands are selectively more cytotoxic toward the cancerous cells than the corresponding noncancerous cells. Computational studies suggested that the adaptive scaffold might allow these ligands to occupy not only the G-quartet planes but also the grooves of the G4DNA.