2-(4-bromobutyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione | 1340583-53-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-bromobutyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione
• CAS: 1340583-53-0
• 化学式: C₁₆H₁₃BrN₂O₄
• 分子量: 377.194
• InChiKey: DPLBEEIUHVVFBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.52
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(4-bromobutyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione 在 氯化亚砜 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-[4-[Bis(2-chloroethyl)amino]butyl]-5-nitrobenzo[de]isoquinoline-1,3-dione
  参考文献：
  名称：

  3-Nitro-naphthalimide and nitrogen mustard conjugate NNM-25 induces hepatocellular carcinoma apoptosis via PARP-1/p53 pathway

  摘要：

  Hepatocellular carcinoma (HCC) is one of the main causes of death in cancer. Some naphthalimide derivatives exert high anti-proliferative effects on HCC. In this study, it is confirmed that 3-nitro-naphthalimide and nitrogen mustard conjugate (NNM-25), a novel compound conjugated by NNM-25, displayed more potent therapeutic action on HCC, both in vivo and in vitro, than amonafide, a naphthalimide drug in clinical trials. More importantly, preliminary toxicological evaluation also supported that NNM-25 exhibited less systemic toxicity than amonafide at the therapeutic dose. The antitumor mechanism of conjugates of naphthalimides with nitrogen mustard remains poorly understood up to now. Here, we first reported that apoptosis might be the terminal fate of cancer cells treated with NNM-25. Inhibition of p53 by siRNA resulted in a significant decrease of NNM-25-induced apoptosis, which corroborated that p53 played a vital role in the cell apoptosis triggered by NNM-25. NNM-25 inhibited the PARP-1 activity, AKT phosphorylation, up-regulated the protein expression of p53, Bad, and mTOR as well as down-regulating the protein expression of Bcl-2 and decreasing mitochondrial membrane potential. It also facilitated cytochrome c release from mitochondria to cytoplasm, activated caspase 8, caspase 9, and caspase 3 in HepG2 cells in vitro, as also authenticated in H22 tumor-bearing mice in vivo. Collectively, the conjugation of naphthalimides with nitrogen mustard provides favorable biological activity and thus is a valuable strategy for future drug design in HCC therapy.

  DOI：

  10.1007/s10495-012-0712-7
• 作为产物：
  描述：

  3-硝基-1,8-萘二甲酸酐 在 ammonium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 20.0h， 生成 2-(4-bromobutyl)-5-nitro-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  新型手性萘二甲酰亚胺-环烷二胺偶联物：设计、合成和抗肿瘤活性

  摘要：

  设计、合成了一系列新型对映体纯萘-环烷二胺偶联物，并评估其对人结肠腺癌 (LoVo)、人肺腺癌 (A549)、人宫颈癌 (Hela) 和人早幼粒细胞白血病细胞系 (HL-60) 的体外细胞毒性）。化合物的细胞毒性高度依赖于环烷基环的大小和相对立体化学以及间隔基的长度。相比之下，对于每对对映异构体都观察到任何种类的对映选择。流式细胞术分析表明，尽管有轻微的细胞凋亡作用，化合物22和23仍可有效诱导前四种细胞系中的G 2 /M 阻滞。

  DOI：

  10.1016/j.bioorg.2021.104859