(S)-2-((((2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxo-4H-chromen-7-yl)oxy)carbonyl)amino)pentanedioic acid

• 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: (S)-2-((((2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxo-4H-chromen-7-yl)oxy)carbonyl)amino)pentanedioic acid
• 英文别名: (2S)-2-[[2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxochromen-7-yl]oxycarbonylamino]pentanedioic acid
• 化学式: C₂₁H₁₇NO₁₂
• 分子量: 475.365
• InChiKey: NWVJBCHKFUEWJQ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  220
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  槲皮素 在 吡啶 、 咪唑 、 盐酸 、 甲醇 、 palladium 10% on activated carbon 、 氨 、 氢气 、 potassium carbonate 、 苯硫酚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二苯醚 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 37.5h， 生成 (S)-2-((((2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxo-4H-chromen-7-yl)oxy)carbonyl)amino)pentanedioic acid
  参考文献：
  名称：

  Water-Soluble and Cleavable Quercetin–Amino Acid Conjugates as Safe Modulators for P-Glycoprotein-Based Multidrug Resistance

  摘要：

  Quercetinamino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetinglutamic acid conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of 0.80.9 mu M. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug-binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of 3a revealed that solubility, stability, and cellular uptake of quercetin were significantly improved by the glutamic acid promoiety, which eventually dissociates from 3a to produce quercetin and quercetin metabolites in intracellular milieu. Taken together, potent MDR-modulating activity along with intracellular conversion into the natural flavonoid quercetin warrants development of the quercetinamino acid conjugates as safe MDR modulators.

  DOI：

  10.1021/jm500290c

文献信息

• Water-Soluble and Cleavable Quercetin–Amino Acid Conjugates as Safe Modulators for P-Glycoprotein-Based Multidrug Resistance
  作者：Mi Kyoung Kim、Hyunah Choo、Youhoon Chong

  DOI：10.1021/jm500290c

  日期：2014.9.11

  Quercetinamino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetinglutamic acid conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of 0.80.9 mu M. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug-binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of 3a revealed that solubility, stability, and cellular uptake of quercetin were significantly improved by the glutamic acid promoiety, which eventually dissociates from 3a to produce quercetin and quercetin metabolites in intracellular milieu. Taken together, potent MDR-modulating activity along with intracellular conversion into the natural flavonoid quercetin warrants development of the quercetinamino acid conjugates as safe MDR modulators.