N,N'-bis(5-hydroxy-3-oxapentyl)-1,6-dibromoperylene-3,4:9,10-tetracarboxylic diimide | 1268493-89-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: N,N'-bis(5-hydroxy-3-oxapentyl)-1,6-dibromoperylene-3,4:9,10-tetracarboxylic diimide
• 英文别名: 11,26-Dibromo-7,18-bis[2-(2-hydroxyethoxy)ethyl]-7,18-diazaheptacyclo[14.6.2.22,5.03,12.04,9.013,23.020,24]hexacosa-1(23),2(26),3,5(25),9,11,13,15,20(24),21-decaene-6,8,17,19-tetrone
• CAS: 1268493-89-5
• 化学式: C₃₂H₂₄Br₂N₂O₈
• 分子量: 724.359
• InChiKey: FTORVKKJCFNBLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N'-bis(5-hydroxy-3-oxapentyl)-1,6-dibromoperylene-3,4:9,10-tetracarboxylic diimide 、 N,N'-bis(5-hydroxy-3-oxapentyl)-1,7-dibromoperylene-3,4:9,10-tetracarboxylic diimide 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N,N'-bis(5-methanesulfonyl-3-oxapentyl)-1,6-dibromoperylene-3,4,9,10-tetracarboxylic diimide 、 N,N'-bis(5-methanesulfonyl-3-oxapentyl)-1,7-dibromoperylene-3,4,9,10-tetracarboxylic diimide
  参考文献：
  名称：

  N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage

  摘要：

  A series of bay-substituted perylene derivatives is reported as a new class of G-quadruplex ligands. The synthesized compounds hive differing N-cyclic substituents on the bay area and differing side chains on the perylene major axis. ESI-MS and FEET measurements highlighted the strongest quadruplex binders in this series and those showing the highest quadruplex/duplex selectivity. Several biological assays were performed on these compounds, which showed that compound 5 (PPL3C) triggered a DNA damage response in transformed cells with the formation of telomeric foci containing phosphorylated gamma-H2AX and 53BP1. This effect mainly occurred in replicating cells and was consistent with Pod dissociation. Compound S does not induce telomere damage in normal cells, which are unaffected by treatment with the: compound, suggesting that this agent preferentially kills cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs.

  DOI：

  10.1021/jm1013665
• 作为产物：
  描述：

  在 甲醇 、 氨 作用下， 以 水 为溶剂， 反应 2.0h， 生成 N,N'-bis(5-hydroxy-3-oxapentyl)-1,6-dibromoperylene-3,4:9,10-tetracarboxylic diimide
  参考文献：
  名称：

  Synthesis of a Dibromoperylene Phosphoramidite Building Block and Its Incorporation at the 5′ End of a G-Quadruplex Forming Oligonucleotide: Spectroscopic Properties and Structural Studies of the Resulting Dibromoperylene Conjugate

  摘要：

  Previous studies indicate that some perylene bisimide derivatives can drive the assembly of DNA G-quadruplexes, thus suggesting the possible advantage in the adoption of perylene-conjugated G-rich oligonucleotides in biological and biotechnological applications. Nevertheless, the typical poor solubility of perylene bisimides strongly limits the number of suitable chemical strategies to prepare perylene-conjugated oligonucleotides. In order to overcome these difficulties, we employed the earlier described core twisted perylene derivatives possessing unique optical and electronic properties, besides good solubility in common solvents. As a first result, the large-scale synthesis of a new dibromoperylene derivative (PEOEBr) phosphoramidite building block is herein reported. Furthermore, the structural behavior of the conjugated PEOEBr-GGGTTAGGG (HTRp2) human telomeric repeat was investigated by using CD, UV, fluorescence, and gel electrophoresis techniques in desalted water and in K+- and Na+-containing buffers. We observed that the peculiar property of PEOEBr moieties to form dimers instead of extended aggregates drives the HTRp2 strands toward dimerization and mainly promotes the formation of quadruplex species having both the 5'-ends located at the same side of the structures. However, the counterions present in solutions (K+ or Na+) as well as the strand concentration, also contribute to influence the topology and the stoichiometry of formed structures. Furthermore, unlike the unmodified sequence GGGTTAGGG (HTR2), HTRp2 strands quickly associate into G-quadruplexes even in desalted water, as assessed by CD experiments.

  DOI：

  10.1021/bc100526q

文献信息

• Synthesis of a Dibromoperylene Phosphoramidite Building Block and Its Incorporation at the 5′ End of a G-Quadruplex Forming Oligonucleotide: Spectroscopic Properties and Structural Studies of the Resulting Dibromoperylene Conjugate
  作者：Marco Franceschin、Nicola Borbone、Giorgia Oliviero、Valentina Casagrande、Maria Scuotto、Teresa Coppola、Silvia Borioni、Luciano Mayol、Giancarlo Ortaggi、Armandodoriano Bianco、Jussara Amato、Michela Varra

  DOI：10.1021/bc100526q

  日期：2011.7.20

  Previous studies indicate that some perylene bisimide derivatives can drive the assembly of DNA G-quadruplexes, thus suggesting the possible advantage in the adoption of perylene-conjugated G-rich oligonucleotides in biological and biotechnological applications. Nevertheless, the typical poor solubility of perylene bisimides strongly limits the number of suitable chemical strategies to prepare perylene-conjugated oligonucleotides. In order to overcome these difficulties, we employed the earlier described core twisted perylene derivatives possessing unique optical and electronic properties, besides good solubility in common solvents. As a first result, the large-scale synthesis of a new dibromoperylene derivative (PEOEBr) phosphoramidite building block is herein reported. Furthermore, the structural behavior of the conjugated PEOEBr-GGGTTAGGG (HTRp2) human telomeric repeat was investigated by using CD, UV, fluorescence, and gel electrophoresis techniques in desalted water and in K+- and Na+-containing buffers. We observed that the peculiar property of PEOEBr moieties to form dimers instead of extended aggregates drives the HTRp2 strands toward dimerization and mainly promotes the formation of quadruplex species having both the 5'-ends located at the same side of the structures. However, the counterions present in solutions (K+ or Na+) as well as the strand concentration, also contribute to influence the topology and the stoichiometry of formed structures. Furthermore, unlike the unmodified sequence GGGTTAGGG (HTR2), HTRp2 strands quickly associate into G-quadruplexes even in desalted water, as assessed by CD experiments.
• <i>N</i>-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage
  作者：Valentina Casagrande、Erica Salvati、Antonello Alvino、Armandodoriano Bianco、Alina Ciammaichella、Carmen D’Angelo、Luca Ginnari-Satriani、Anna Maria Serrilli、Sara Iachettini、Carlo Leonetti、Stephen Neidle、Giancarlo Ortaggi、Manuela Porru、Angela Rizzo、Marco Franceschin、Annamaria Biroccio

  DOI：10.1021/jm1013665

  日期：2011.3.10

  A series of bay-substituted perylene derivatives is reported as a new class of G-quadruplex ligands. The synthesized compounds hive differing N-cyclic substituents on the bay area and differing side chains on the perylene major axis. ESI-MS and FEET measurements highlighted the strongest quadruplex binders in this series and those showing the highest quadruplex/duplex selectivity. Several biological assays were performed on these compounds, which showed that compound 5 (PPL3C) triggered a DNA damage response in transformed cells with the formation of telomeric foci containing phosphorylated gamma-H2AX and 53BP1. This effect mainly occurred in replicating cells and was consistent with Pod dissociation. Compound S does not induce telomere damage in normal cells, which are unaffected by treatment with the: compound, suggesting that this agent preferentially kills cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs.