1,7-bis(3-methoxyphenyl)-1,6-heptadiene-3,5-dione

• 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: 1,7-bis(3-methoxyphenyl)-1,6-heptadiene-3,5-dione
• 英文别名: bisdemethoxycurcumin；1,7-bis((E)-3-methoxyphenyl)-1,6-heptadien-3,5-dione；(1E,6E)-1,7-bis(3-methoxyphenyl)hepta-1,6-diene-3,5-dione
• 化学式: C₂₁H₂₀O₄
• 分子量: 336.387
• InChiKey: WSJHJHWGIOGUSG-WGDLNXRISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,7-bis(3-methoxyphenyl)-1,6-heptadiene-3,5-dione 在 一水合肼 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以41%的产率得到3,5-bis[(1E)-2-(3-methoxyphenyl)ethenyl]-1H-pyrazole
  参考文献：
  名称：

  结合微管蛋白的3,5-双（苯乙烯基）吡唑类化合物作为治疗去势抵抗性前列腺癌的先导化合物。

  摘要：

  微管结合紫杉烷类，多西他赛和卡巴他赛通过静脉内给药治疗去势抵抗性前列腺癌（CRPC），因为这些药物的低和高度可变的生物利用度极大地阻碍了这些药物的口服给药。使用简单，快速且环保的微波辅助方案，我们合成了许多3,5-双（苯乙烯基）吡唑2a-1，因此可以筛选它们在不依赖雄激素的PC3前列腺癌细胞中的抗增殖活性。线。令人惊讶的是，这些结构简单的3,5-双（苯乙烯基）吡唑类化合物（2a和2l）中的两个在PC3细胞系的低微摩尔范围内具有50％的最大细胞增殖抑制（GI50）浓度，因此是选择用于进一步的生物学评估（细胞凋亡和细胞周期分析，以及对微管蛋白和微管的影响）。从这些研究中我们的发现表明，3,5-双[（1E）-2（2,6-二氯苯基）乙烯基] -1H-吡唑2l 1）对PC3细胞的细胞周期产生了显着影响，其中绝大多数G2 / M期的已处理细胞（89％）；2）即使去除了该化合物，仍会诱导PC3细胞死亡。3）与微管蛋白结合[解离常数（Kd）0

  DOI：

  10.1124/mol.119.118539
• 作为产物：
  描述：

  3-甲氧基苯甲醛 、 乙酰丙酮 在 boron trioxide 、 硼酸三丁酯 、 正丁胺 作用下， 以 乙酸乙酯 为溶剂， 反应 5.0h， 以42%的产率得到1,7-bis(3-methoxyphenyl)-1,6-heptadiene-3,5-dione
  参考文献：
  名称：

  3,3′-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway

  摘要：

  In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3'-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3'-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO center dot) and H2O2. The more cytotoxic activity and ROS-generating ability of 1b may be due to the more stable in (RPMI)-1640 medium and more massive uptake than curcumin. Then the generation of ROS can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 3,3'-hydroxy curcumin (1b) may cause HepG2 cells apoptosis through ROS-mediated pathway, but also offer an important information for design of curcumin analog. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.019

文献信息

• Identification of a new curcumin synthase from ginger and construction of a curcuminoid-producing unnatural fusion protein diketide-CoA synthase::curcumin synthase
  作者：Le Zhang、Bowen Gao、Xiaohui Wang、Zhongxiu Zhang、Xiao Liu、Juan Wang、Ting Mo、Yuyu Liu、Shepo Shi、Pengfei Tu

  DOI：10.1039/c5ra23401h

  日期：——

  The new curcumin synthase and the unnatural fusion protein reported here are useful for metabolic engineering of pharmaceutically important curcuminoids.

  这里报告的新型姜黄素合成酶和非自然融合蛋白质，对于代谢工程制备重要的药用姜黄素具有实用价值。
• THERAPEUTIC COMPOSITIONS COMPRISING A COMBINATION OF A HARMINE AND ISOVANILLIN COMPONENT
  申请人：Ions Pharmaceutical S.À R.L.

  公开号：EP3275465A1

  公开（公告）日：2018-01-31

  Human therapeutic treatment compositions comprise the combination of at least one harmine component, and at least one isovanillin component, wherein the components of the composition are different. The compositions are effective for the treatment of human conditions, especially human cancers.

  人类治疗组合物由至少一种禾本科成分和至少一种异香兰素成分组合而成，其中组合物的成分各不相同。这些组合物可有效治疗人类疾病，尤其是人类癌症。
• Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof
  申请人：Ankh Life Sciences Limited

  公开号：US10471049B2

  公开（公告）日：2019-11-12

  Human therapeutic treatment compositions comprise at least two of a curcumin component, a harmine component, and an isovanillin component, and preferably all three in combination. The agents are effective for the treatment of human conditions, especially human cancers.

  人类治疗组合物包含姜黄素成分、禾本科成分和异香兰素成分中的至少两种，最好是三种成分的组合。这些制剂可有效治疗人类疾病，尤其是人类癌症。
• Human therapeutic agents
  申请人：Ankh Life Sciences Limited

  公开号：US10744124B2

  公开（公告）日：2020-08-18

  Human therapeutic treatment compositions comprise at least two of a curcumin component, a harmine component, and an isovanillin component, and preferably all three in combination. The agents are effective for the treatment of human conditions, especially human cancers.

  人类治疗组合物包含姜黄素成分、禾本科成分和异香兰素成分中的至少两种，最好是三种成分的组合。这些制剂可有效治疗人类疾病，尤其是人类癌症。
• Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
  作者：Lorraine M. Deck、Lucy A. Hunsaker、Thomas A. Vander Jagt、Lisa J. Whalen、Robert E. Royer、David L. Vander Jagt

  DOI：10.1016/j.ejmech.2017.11.048

  日期：2018.1

  Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability, to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. (C) 2017 Published by Elsevier Masson SAS.