3,6-bis[3-(heptamethyleneimino)propionamido]acridine

• 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: 3,6-bis[3-(heptamethyleneimino)propionamido]acridine
• 英文别名: 3,6-Bis[3-(heptamethyleneimino)piperizinopropionamido)acridine；3-(azocan-1-yl)-N-[6-[3-(azocan-1-yl)propanoylamino]acridin-3-yl]propanamide
• 化学式: C₃₃H₄₅N₅O₂
• 分子量: 543.753
• InChiKey: KGEMXWJLGMFZFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  原黄素 在 sodium iodide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 3,6-bis[3-(heptamethyleneimino)propionamido]acridine
  参考文献：
  名称：

  Molecular Modeling Studies on G-Quadruplex Complexes of Telomerase Inhibitors:  Structure−Activity Relationships

  摘要：

  Inhibition of the ability of the enzyme telomerase to add telomeric repeats to the end of chromosomes is a novel target for potential anticancer therapy. This paper examines the hypothesis that compounds possessing a planar aromatic chromophore inhibit telomerase via stabilization of, and binding to, a folded guanine quadruplex structure. Two series of telomerase inhibitors have been designed based on the 2,6-disubstituted amidoanthracene-9,10-dione and a,6-disubstituted acridine chromophores in order to investigate structure-activity relationships between biological activity and substituent group size. The relative binding energies between these compounds and the folded human telomere DNA quadruplex were determined using molecular simulation methods, involving explicitly solvated structures. The results obtained are in excellent agreement with the biological activity as measured in vitro using a modified TRAP assay and in general agreement with the ranking order of binding enthalpies found in isothermal titration calorimetry studies. This broad agreement provides strong support for the hypothesis that guanine quadruplexes are the primary target for telomerase inhibitors with extended planar chromophores.

  DOI：

  10.1021/jm990287e

文献信息

• Human telomerase inhibition by substituted acridine derivatives
  作者：R. John Harrison、Sharon M. Gowan、Lloyd R. Kelland、Stephen Neidle

  DOI：10.1016/s0960-894x(99)00394-7

  日期：1999.9

  A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 mu M, comparable to their cytotoxicity in ovarian cancer cell lines. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Molecular Modeling Studies on G-Quadruplex Complexes of Telomerase Inhibitors:  Structure−Activity Relationships
  作者：Martin A. Read、Alexis A. Wood、John R. Harrison、Sharon M. Gowan、Lloyd R. Kelland、Harvinder S. Dosanjh、Stephen Neidle

  DOI：10.1021/jm990287e

  日期：1999.11.1

  Inhibition of the ability of the enzyme telomerase to add telomeric repeats to the end of chromosomes is a novel target for potential anticancer therapy. This paper examines the hypothesis that compounds possessing a planar aromatic chromophore inhibit telomerase via stabilization of, and binding to, a folded guanine quadruplex structure. Two series of telomerase inhibitors have been designed based on the 2,6-disubstituted amidoanthracene-9,10-dione and a,6-disubstituted acridine chromophores in order to investigate structure-activity relationships between biological activity and substituent group size. The relative binding energies between these compounds and the folded human telomere DNA quadruplex were determined using molecular simulation methods, involving explicitly solvated structures. The results obtained are in excellent agreement with the biological activity as measured in vitro using a modified TRAP assay and in general agreement with the ranking order of binding enthalpies found in isothermal titration calorimetry studies. This broad agreement provides strong support for the hypothesis that guanine quadruplexes are the primary target for telomerase inhibitors with extended planar chromophores.