3,5-bis(4-hydroxy-3-methoxystyryl)-1-(4-methoxyphenyl)pyrazole

• 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: 3,5-bis(4-hydroxy-3-methoxystyryl)-1-(4-methoxyphenyl)pyrazole
• 英文别名: 4,4′-((1E,1′E)-2,2′-(1-(4-methoxyphenyl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl))bis(2-methoxyphenol)；4,4'-((1E,1'E)-(1-(4-methoxyphenyl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl))bis(2-methoxyphenol)；N-(4-Methoxyphenylpyrazole)Curcumin；4-[(E)-2-[5-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-(4-methoxyphenyl)pyrazol-3-yl]ethenyl]-2-methoxyphenol
• 化学式: C₂₈H₂₆N₂O₅
• 分子量: 470.525
• InChiKey: FPMPHNSCFMDHQM-KBXRYBNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  乙酰丙酮 在 硼酸 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.2h， 生成 3,5-bis(4-hydroxy-3-methoxystyryl)-1-(4-methoxyphenyl)pyrazole
  参考文献：
  名称：

  姜黄素模板化唑的机械化学合成及抗氧化活性

  摘要：

  一种在室温下合成姜黄素（1）衍生的 3,5-双（苯乙烯基）吡唑和 3,5-双（苯乙烯基）异恶唑（2a-g）的无溶剂机械化学方法，反应时间非常短，被报道。姜黄素的这种早期结构修饰，通过将其转化为等排吡唑或异恶唑单元，在其 β-二酮单元上需要长时间加热。基于 DPPH、FRAP 和 β-胡萝卜素漂白试验对这些化合物的抗氧化活性进行的评估表明，这些唑类中有几种是比姜黄素更好的抗氧化剂，其中异恶唑衍生物 2g 总体上是最好的。通常，姜黄素 (1)、3,5-双(4-羟基-3-甲氧基苯乙烯基)吡唑 (2a) 对 2,2-二苯基-1-苦基肼 (10-2 mmol)（以 EC50 值表示）的抑制作用, 3,5-双(4-羟基-3-甲氧基苯乙烯基)异恶唑 (2g) 为 40 ± 0.06, 分别为 14 ± 0.18 和 8 ± 0.11 μmol。此外，所报告的方法可用于获取 3,5-双（4-羟基-3-甲氧基苯乙烯基）-1-苯基吡唑

  DOI：

  10.1002/ardp.201500305

文献信息

• Synthesis and antiproliferative studies of curcumin pyrazole derivatives
  作者：Honnalagere Ramesh Puneeth、Hanumappa Ananda、Kothanahally S. Sharath Kumar、Kanchugarakoppal S. Rangappa、Angatahally Chandrashekariah Sharada

  DOI：10.1007/s00044-016-1628-5

  日期：2016.9

  exhibited a high degree of cytotoxicity against cancer cells and minimum growth inhibitory effects against normal cells HEK293T and hence further, cell cycle analysis and mitochondrial membrane potential studies (JC-1 assay) were conducted by utilizing flow cytometry against K562 cells. This compound effectively arrested cell cycle progression at SubG1 phase and cells exhibited decreased membrane potential

  合成了一系列姜黄素吡唑衍生物（3a–e）。通过1 H和13 C NMR光谱技术确定化学结构，并通过LC-MS和熔点测定法确认其纯度。通过MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）测定法筛选化合物对不同癌细胞系的抗癌作用。类似物证明对MCF-7，HeLa和K562细胞系具有明显的IC 50值生长抑制作用。化合物3b对癌细胞具有高度的细胞毒性，并且对正常细胞HEK293T的生长抑制作用最小，因此，进一步利用流式细胞术对K562细胞进行了细胞周期分析和线粒体膜电位研究（JC-1分析）。该化合物有效地阻止了SubG1期的细胞周期进程，并且细胞以浓度依赖的方式显示出降低的膜电位，并且荧光从红色变为绿色。我们的发现表明，化合物3b可能是一种有前途的抗癌药，因为它可以有效抑制细胞增殖，并可以选择用于进一步的体外和体内研究。
• Synthesis and exploration of novel curcumin analogues as anti-malarial agents
  作者：Satyendra Mishra、Krishanpal Karmodiya、Namita Surolia、Avadhesha Surolia

  DOI：10.1016/j.bmc.2007.12.054

  日期：2008.3.15

  Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of similar to 3.25 mu M (MIC = 13.2 mu M) and IC50 4.21 mu M (MIC = 14.4 mu M), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 mu M and CQ-R P. falcipartan at IC50 of 0.45 mu M, 0.89, 0.75 mu M, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falcipartan inhibitors and promising candidates for the design of novel anti-malarial agents. (C) 2007 Elsevier Ltd. All rights reserved.
• Activation of anti-oxidant of curcumin pyrazole derivatives through preservation of mitochondria function and Nrf2 signaling pathway
  作者：Liping Liao、Jinguo Shi、Caibao Jiang、Liantao Zhang、Lisi Feng、Jiayong Liu、Jingxia Zhang

  DOI：10.1016/j.neuint.2019.01.026

  日期：2019.5

  Oxidative stress is an important cause of neurodegenerative diseases. Antioxidant is an potential important method to treat such diseases. The aim of this study is to discover new and effective antioxidants and their mechanism. The neuroprotective effect of six curcumin pyrozole compounds were first evaluated on sodium nitroprusside (SNP) - induced PC12 cell injury by testing cell viability and LDH release. The results showed that four compounds (C1-C4) have more significant protective effects compared to curcumin and edaravone. Furthermore, compounds C1-C4 can attenuate the intracellular ROS, and compound C3 is the most effective one which can preservate the mitochondria function by inhibiting the mitochondrial membrane potential loss and enhance nuclear translocation of Nrf2 in PC12 cell. These results indicated that C3 may be a potential candidate drug for treating neurodegenerative diseases.
• Mechanochemical Synthesis and Antioxidant Activity of Curcumin-Templated Azoles
  作者：Daisy R. Sherin、Kallikat N. Rajasekharan

  DOI：10.1002/ardp.201500305

  日期：2015.12

  solvent‐free, mechanochemical method for the synthesis of curcumin (1) derived 3,5‐bis(styryl)pyrazoles and 3,5‐bis(styryl)isoxazole (2a–g) at room temperature, with very short reaction time, is reported. Such earlier structural modifications of curcumin, at its β‐diketone unit by transforming it into an isosteric pyrazole or isoxazole unit, required prolonged heating. The evaluation of the antioxidant activity

  一种在室温下合成姜黄素（1）衍生的 3,5-双（苯乙烯基）吡唑和 3,5-双（苯乙烯基）异恶唑（2a-g）的无溶剂机械化学方法，反应时间非常短，被报道。姜黄素的这种早期结构修饰，通过将其转化为等排吡唑或异恶唑单元，在其 β-二酮单元上需要长时间加热。基于 DPPH、FRAP 和 β-胡萝卜素漂白试验对这些化合物的抗氧化活性进行的评估表明，这些唑类中有几种是比姜黄素更好的抗氧化剂，其中异恶唑衍生物 2g 总体上是最好的。通常，姜黄素 (1)、3,5-双(4-羟基-3-甲氧基苯乙烯基)吡唑 (2a) 对 2,2-二苯基-1-苦基肼 (10-2 mmol)（以 EC50 值表示）的抑制作用, 3,5-双(4-羟基-3-甲氧基苯乙烯基)异恶唑 (2g) 为 40 ± 0.06, 分别为 14 ± 0.18 和 8 ± 0.11 μmol。此外，所报告的方法可用于获取 3,5-双（4-羟基-3-甲氧基苯乙烯基）-1-苯基吡唑