6-Ethyl-2-[4-[2-[2-[2-[2-[4-(6-ethyl-4-oxochromen-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]chromen-4-one | 1167577-31-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 6-Ethyl-2-[4-[2-[2-[2-[2-[4-(6-ethyl-4-oxochromen-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]chromen-4-one
• CAS: 1167577-31-2
• 化学式: C₄₂H₄₂O₉
• 分子量: 690.79
• InChiKey: XUCRYSQMVLUNBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1,11-二(甲烷磺酰基氧基)-3,6,9-三氧杂十一烷 、 6-乙基-2-(4-羟基苯基)-4H-苯并吡喃-4-酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-Ethyl-2-[4-[2-[2-[2-[2-[4-(6-ethyl-4-oxochromen-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]chromen-4-one
  参考文献：
  名称：

  Modulation of Multidrug Resistance Protein 1 (MRP1/ABCC1)-Mediated Multidrug Resistance by Bivalent Apigenin Homodimers and Their Derivatives

  摘要：

  Here we showed that bivalency approach is effective in modulating multidrug resistance protein 1 (MRP1/ABCC1)-mediated doxorubicin (DOX) and etoposide (VP16) resistance in human 2008/MRP1 ovarian carcinoma cells. Flavonoid dimers bearing five or six ethylene glycol (EG) units with 6-methyl (4e, 4f) or 7-methyl (5e, 5f) substitution on the ring A of flavonoid dimers have the highest modulating activity for DOX against MRP1 with an EC50 ranging from 73 to 133 nM. At 0.5 mu M, the flavonoid dimer 4e was sufficient to restore DOX accumulation in 2008/MRP1 to parental 2008/P level. Lineweaver-Burk and Dixon plot suggested that it is likely a competitive inhibitor of DOX transport with a K-i = 0.2 mu M. Our data suggest that flavonoid dimers have a high affinity toward binding to DOX recognition site of MRP1. This results in inhibiting DOX transport, increasing intracellular DOX retention, and finally resensitizing 2008/MRP1 to DOX. The present study demonstrates that flavonoid dimers can be employed as an effective modulator of MRP1-mediated drug resistance in cancer cells.

  DOI：

  10.1021/jm900194w

文献信息

• Modulation of Multidrug Resistance Protein 1 (MRP1/ABCC1)-Mediated Multidrug Resistance by Bivalent Apigenin Homodimers and Their Derivatives
  作者：Iris L. K. Wong、Kin-Fai Chan、Ka Hing Tsang、Chi Yin Lam、Yunzhe Zhao、Tak Hang Chan、Larry Ming Cheung Chow

  DOI：10.1021/jm900194w

  日期：2009.9.10

  Here we showed that bivalency approach is effective in modulating multidrug resistance protein 1 (MRP1/ABCC1)-mediated doxorubicin (DOX) and etoposide (VP16) resistance in human 2008/MRP1 ovarian carcinoma cells. Flavonoid dimers bearing five or six ethylene glycol (EG) units with 6-methyl (4e, 4f) or 7-methyl (5e, 5f) substitution on the ring A of flavonoid dimers have the highest modulating activity for DOX against MRP1 with an EC50 ranging from 73 to 133 nM. At 0.5 mu M, the flavonoid dimer 4e was sufficient to restore DOX accumulation in 2008/MRP1 to parental 2008/P level. Lineweaver-Burk and Dixon plot suggested that it is likely a competitive inhibitor of DOX transport with a K-i = 0.2 mu M. Our data suggest that flavonoid dimers have a high affinity toward binding to DOX recognition site of MRP1. This results in inhibiting DOX transport, increasing intracellular DOX retention, and finally resensitizing 2008/MRP1 to DOX. The present study demonstrates that flavonoid dimers can be employed as an effective modulator of MRP1-mediated drug resistance in cancer cells.