7-(benzo[d][1,3]dioxol-5-yl)-3-ethyl-3H-pyrrolo[3,2-f]quinolin-9(6H)-one

• 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: 7-(benzo[d][1,3]dioxol-5-yl)-3-ethyl-3H-pyrrolo[3,2-f]quinolin-9(6H)-one
• 英文别名: 7-(1,3-benzodioxol-5-yl)-3-ethyl-6H-pyrrolo[3,2-f]quinolin-9-one
• 化学式: C₂₀H₁₆N₂O₃
• 分子量: 332.359
• InChiKey: CMINJRRFMVFFIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-亚甲二氧苯乙酮 在 sodium hydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二苯醚 、 乙醇 、 甲苯 、 mineral oil 为溶剂， 反应 48.25h， 生成 7-(benzo[d][1,3]dioxol-5-yl)-3-ethyl-3H-pyrrolo[3,2-f]quinolin-9(6H)-one
  参考文献：
  名称：

  Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs

  摘要：

  Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI(50) values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial. transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of beta-tubulin. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.038

文献信息

• Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs
  作者：Roberta Bortolozzi、Elena Mattiuzzo、Matteo Dal Pra、Mattia Sturlese、Stefano Moro、Ernest Hamel、Davide Carta、Giampietro Viola、Maria Grazia Ferlin

  DOI：10.1016/j.ejmech.2017.11.038

  日期：2018.1

  Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI(50) values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial. transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of beta-tubulin. (C) 2017 Elsevier Masson SAS. All rights reserved.