5-hydroxy-7-(4-hydroxyl-3-methoxyphenyl)-1-(4-hydroxylphenyl)-3-heptanone | 908094-05-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 5-hydroxy-7-(4-hydroxyl-3-methoxyphenyl)-1-(4-hydroxylphenyl)-3-heptanone
• 英文别名: 5-Hydroxy-1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxylphenyl)-3-heptanone；5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptan-3-one
• CAS: 908094-05-3
• 化学式: C₂₀H₂₄O₅
• 分子量: 344.408
• InChiKey: WAHUIEHYVBLIER-UHFFFAOYSA-N

物化性质

• 沸点：
  601.9±55.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  四氢脱甲氧基二阿魏酰甲烷 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 5-hydroxy-7-(4-hydroxyl-3-methoxyphenyl)-1-(4-hydroxylphenyl)-3-heptanone 、 5-Hydroxy-7-(4-hydroxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)-3-heptanone
  参考文献：
  名称：

  Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species

  摘要：

  The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Tryponosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 mu M, respectively). Among 43 curcuminoid analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in sub-micromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxy-phenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 +/- 0.007 mu M; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 +/- 0.01 mu M). Using a previously characterized diminazene-resistant T. b, brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against 7: b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 +/- 3 and 37 +/- 6 mu M. respectively) while the control drug, pentamidine, displayed an EC50 of 16 +/- 2 mu M. Among the active curcuminoid analogs, four Compounds exhibited EC50 values of less than 5 mu M against Leishmania major promastigotes and four against L mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.11.035

文献信息

• Curcuminoid analogs inhibit nitric oxide production from LPS-activated microglial cells
  作者：Jiraporn Tocharus、Sataporn Jamsuwan、Chainarong Tocharus、Chatchawan Changtam、Apichart Suksamrarn

  DOI：10.1007/s11418-011-0599-6

  日期：2012.4

  The chemically modified analogs, the demethylated analogs 4–6, the tetrahydro analogs 7–9 and the hexahydro analogs 10–12, of curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) were evaluated for their inhibitory activity on lipopolysaccharide activated nitric oxide (NO) production in HAPI microglial cells. Di-O-demethylcurcumin (5) and O-demethyldemethoxycurcumin (6) are the two most

  对姜黄素 ( 1 )、脱甲氧基姜黄素( 2 ) 和双脱甲氧基姜黄素 ( 3 )的化学修饰类似物、去甲基化类似物4 – 6、四氢类似物7 – 9和六氢类似物10 – 12对脂多糖活化的抑制活性进行了评估HAPI 小胶质细胞中一氧化氮 (NO) 的产生。Di- O-去甲基姜黄素 ( 5 ) 和O-去甲基去甲氧基姜黄素 ( 6 ) 是抑制 NO 生成的两种最有效的化合物。类似物5和6分别比母体姜黄素1和2 的活性高两倍或几乎两倍。此外，这两种化合物抑制了诱导型 NO 合酶的 mRNA 表达水平。类似物5和6的强大神经保护活性提供了潜在的替代化合物，可作为与活化小胶质细胞相关的神经系统疾病的治疗剂进行开发。
• Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species
  作者：Chatchawan Changtam、Harry P. de Koning、Hasan Ibrahim、M. Sohail Sajid、Matthew K. Gould、Apichart Suksamrarn

  DOI：10.1016/j.ejmech.2009.11.035

  日期：2010.3

  The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Tryponosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 mu M, respectively). Among 43 curcuminoid analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in sub-micromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxy-phenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 +/- 0.007 mu M; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 +/- 0.01 mu M). Using a previously characterized diminazene-resistant T. b, brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against 7: b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 +/- 3 and 37 +/- 6 mu M. respectively) while the control drug, pentamidine, displayed an EC50 of 16 +/- 2 mu M. Among the active curcuminoid analogs, four Compounds exhibited EC50 values of less than 5 mu M against Leishmania major promastigotes and four against L mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold. (C) 2009 Elsevier Masson SAS. All rights reserved.

表征谱图