(2E)-1-(2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one | 1228673-65-1

• 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: (2E)-1-(2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one
• 英文别名: 3-methoxyxanthohumol；(E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one
• CAS: 1228673-65-1
• 化学式: C₂₂H₂₄O₆
• 分子量: 384.429
• InChiKey: DBKNCZHFQQYVGW-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2,4-bis(methoxymethoxy)-6-((3-methylbut-2-en-1-yl)oxy)phenyl)ethanone 在 盐酸 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基苯胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.58h， 生成 (2E)-1-(2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one
  参考文献：
  名称：

  Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent

  摘要：

  The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 mu M). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.

  DOI：

  10.1021/jm5016507

文献信息

• Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect
  作者：Susanne Vogel、Matej Barbic、Guido Jürgenliemk、Jörg Heilmann

  DOI：10.1016/j.ejmech.2010.01.060

  日期：2010.6

  Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'-dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'-trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3 +/- 04 mu M. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7 +/- 0.3 and 6.0 +/- 1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 mu M the TNF alpha induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.