8-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)octanoic acid | 936943-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 8-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)octanoic acid
• CAS: 936943-57-6
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: XEPKRYWUYKHGLZ-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  8-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)octanoic acid 、 N-[5-[[5-[3-[3-aminopropyl(methyl)amino]propylcarbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylimidazole-2-carboxamide 在 氯化亚砜 、 TEA 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 144.42h， 以30%的产率得到N-[5-[[5-[3-[3-[8-(1,3-dioxobenzo[de]isoquinolin-2-yl)octanoylamino]propyl-methylamino]propylcarbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylimidazole-2-carboxamide
  参考文献：
  名称：

  Targeting the inverted CCAAT Box-2 of the topoisomerase IIα gene: DNA sequence selective recognition by a polyamide–intercalator as a staggered dimer

  摘要：

  The synthesis and DNA binding characteristics of a polyamide-intercalator conjugate, designed to inhibit NF-Y binding to the ICB-2 site of the topoisomerase IIa promoter and up-regulate the expression of the enzyme in confluent cells, are reported. Thermal denaturation and CD titration studies demonstrated binding to the cognate sequence (5'-AAGCTA-3'). Formation of ligand-induced CD bands at similar to 330 nm provided indication that the molecule interacts selectively in the minor groove of DNA. Intercalation was evidenced by a fivefold increase in emission of the intercalator moiety upon binding to the ICB-2 hairpin oligonucleotide. An increase in viscosity of a solution of calf-thymus DNA on addition of the conjugate provided further evidence. The binding affinity of the conjugate was ascertained using SPR (5.6 x 10(6) M(-1)), which according to a gel shift assay was capable of inhibiting the binding of NF-Y at a concentration of 50 mu M. DNaseI footprinting, using the topoII alpha promoter sequence, highlighted the specificity of the conjugate for the cognate site (5'-AAGCTA-3'). Finally, through Western blot analysis, confluent murine NIH 3T3 cells treated with conjugate were found to have enhanced expression of topoIIa. These results suggest that the conjugate can enter the nucleus, bind to its target site, presumably as a stacked dimer, and up-regulate the expression of topoIIa by blocking the binding of NF-Y. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.059