2'-hydroxy-2,4',6-trimethoxychalcone | 445284-62-8

• 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: 2'-hydroxy-2,4',6-trimethoxychalcone
• 英文别名: 3-(2,6-dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• CAS: 445284-62-8
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: ZCBBKYSIMWEHKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.99
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  丹皮酚 、 2,6-二甲氧基苯甲醛 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以80%的产率得到2'-hydroxy-2,4',6-trimethoxychalcone
  参考文献：
  名称：

  A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

  摘要：

  Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2',5'-dihydroxychalcone (2',5'-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure-activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F andCl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.

  DOI：

  10.1021/jm2016073

文献信息

• Investigation of Chalcones as Selective Inhibitors of the Breast Cancer Resistance Protein: Critical Role of Methoxylation in both Inhibition Potency and Cytotoxicity
  作者：Glaucio Valdameri、Charlotte Gauthier、Raphaël Terreux、Rémy Kachadourian、Brian J. Day、Sheila M. B. Winnischofer、Maria E. M. Rocha、Véronique Frachet、Xavier Ronot、Attilio Di Pietro、Ahcène Boumendjel

  DOI：10.1021/jm2016528

  日期：2012.4.12

  ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 mu M and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6'-hydroxyl-2',4'-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.