3-(4-Ethoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one | 76554-22-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(4-Ethoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one
• CAS: 76554-22-8
• 化学式: C₁₉H₂₀O₅
• 分子量: 328.365
• InChiKey: BCBTTXMSVCLDKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-Ethoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one 在 碘 作用下， 以 二甲基亚砜 为溶剂， 生成 5,7-dimethoxy-4'-ethoxyflavone
  参考文献：
  名称：

  Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux

  摘要：

  The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of cancer cells by mediating drug efflux out of cells, often in co-transport with glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells. That phenomenon takes place in the more global anticancer strategy called "collateral sensitivity" and could be exploited to eradicate some chemoresistant cancer cells. Seeking alternative compounds to verapamil, we screened a library of natural flavonoids and synthetic derivatives. A large number of these compounds stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated for their cytotoxic effect on MRP1-overexpressing cells versus parental cells. Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading them to apoptosis. However, some others do not exhibit any cytotoxicity while promoting a strong GSH efflux, indicating that GSH efflux is necessary but not sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure activity relationships show that the absence of a hydroxyl group at position 3 of the flavonoid C ring is an absolute requirement for induction of MRP1-cells death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells with a IC50 value of 4.1 mu M for compound 11 and 4.9 mu M for chrysin and compound 22, making them among the best described selective killer compounds of multidrug ABC transporter-overexpressing cells. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.05.017
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 、 4-乙氧基苯甲醛 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 3-(4-Ethoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux

  摘要：

  The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of cancer cells by mediating drug efflux out of cells, often in co-transport with glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells. That phenomenon takes place in the more global anticancer strategy called "collateral sensitivity" and could be exploited to eradicate some chemoresistant cancer cells. Seeking alternative compounds to verapamil, we screened a library of natural flavonoids and synthetic derivatives. A large number of these compounds stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated for their cytotoxic effect on MRP1-overexpressing cells versus parental cells. Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading them to apoptosis. However, some others do not exhibit any cytotoxicity while promoting a strong GSH efflux, indicating that GSH efflux is necessary but not sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure activity relationships show that the absence of a hydroxyl group at position 3 of the flavonoid C ring is an absolute requirement for induction of MRP1-cells death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells with a IC50 value of 4.1 mu M for compound 11 and 4.9 mu M for chrysin and compound 22, making them among the best described selective killer compounds of multidrug ABC transporter-overexpressing cells. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.05.017

文献信息

• Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux
  作者：Doriane Lorendeau、Lauriane Dury、Estelle Genoux-Bastide、Florine Lecerf-Schmidt、Claudia Simões-Pires、Pierre-Alain Carrupt、Raphaël Terreux、Sandrine Magnard、Attilio Di Pietro、Ahcène Boumendjel、Hélène Baubichon-Cortay

  DOI：10.1016/j.bcp.2014.05.017

  日期：2014.8

  The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of cancer cells by mediating drug efflux out of cells, often in co-transport with glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells. That phenomenon takes place in the more global anticancer strategy called "collateral sensitivity" and could be exploited to eradicate some chemoresistant cancer cells. Seeking alternative compounds to verapamil, we screened a library of natural flavonoids and synthetic derivatives. A large number of these compounds stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated for their cytotoxic effect on MRP1-overexpressing cells versus parental cells. Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading them to apoptosis. However, some others do not exhibit any cytotoxicity while promoting a strong GSH efflux, indicating that GSH efflux is necessary but not sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure activity relationships show that the absence of a hydroxyl group at position 3 of the flavonoid C ring is an absolute requirement for induction of MRP1-cells death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells with a IC50 value of 4.1 mu M for compound 11 and 4.9 mu M for chrysin and compound 22, making them among the best described selective killer compounds of multidrug ABC transporter-overexpressing cells. (C) 2014 Elsevier Inc. All rights reserved.