5-[(1E,3E)-4-(4-hydroxyphenyl)-1,3-butadienyl]-1,3-benzenediol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-[(1E,3E)-4-(4-hydroxyphenyl)-1,3-butadienyl]-1,3-benzenediol
• 英文别名: trans,trans-3,5,4'-trihydroxybistyryl；5-[(1E,3E)-4-(4-hydroxyphenyl)buta-1,3-dienyl]benzene-1,3-diol
• 化学式: C₁₆H₁₄O₃
• 分子量: 254.285
• InChiKey: OTIFOXGFOBXFRX-ZPUQHVIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对甲苯甲醚 在 N-溴代丁二酰亚胺(NBS) 、 甲基碘化镁 、 偶氮二异丁腈 、 potassium tert-butylate 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.17h， 生成 5-[(1E,3E)-4-(4-hydroxyphenyl)-1,3-butadienyl]-1,3-benzenediol
  参考文献：
  名称：

  Engineered Chimeric Enzymes as Tools for Drug Discovery:  Generating Reliable Bacterial Screens for the Detection, Discovery, and Assessment of Estrogen Receptor Modulators

  摘要：

  Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.

  DOI：

  10.1021/ja067754j

文献信息

• New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription
  作者：Carolina Villalonga-Barber、Aggeliki K. Meligova、Xanthippi Alexi、Barry R. Steele、Constantinos E. Kouzinos、Constantinos G. Screttas、Efrosini S. Katsanou、Maria Micha-Screttas、Michael N. Alexis

  DOI：10.1016/j.bmc.2010.11.018

  日期：2011.1

  100 to 400-fold more potent than resveratrol. Derivatives 2, 4 and 6 lacked cytotoxic activity against HT22 cells and estrogen receptor agonist or antagonist activity in estrogen response element-dependent gene expression and in estrogen-dependent proliferation of MCF-7 human breast cancer cells. In addition, they were incapable of interfering with aryl hydrocarbon receptor-mediated xenobiotic response

  我们合成了一系列新的（E）二苯乙烯类衍生物，其在与反式-白藜芦醇的环位置相同或相似的环位置上含有羟基，并带有一个或两个与4'-OH邻位的给电子基团，我们已经使用它们评估了它们的神经保护活性。谷氨酸攻击的HT22海马神经元可模拟氧化应激诱导的神经元细胞死亡。活性最高的衍生物5-（E）-2- [3,5-双（1-乙基丙基）-4-羟苯基]乙烯基} -1,3-苯二醇（2），5-[（E）-2 -（（3,5-二叔丁基-4-羟基苯基乙烯基）]-1,3-苯二醇（4）和5-（1 E，3 E）-4- [3,5-双（1-乙基丙基）-4-羟基苯基] -1,3-丁二烯基} -1,3-苯二醇（6）的EC 50值分别为30、45和12 nM。 ，并且是。效力比白藜芦醇高100到400倍。衍生物2，4和6缺乏细胞毒性活性对HT22细胞和雌激素反应元件依赖性基因表达雌激素受体激动剂或拮抗剂活性，并在MCF-7人乳腺癌细胞
• Finding more active antioxidants and cancer chemoprevention agents by elongating the conjugated links of resveratrol
  作者：Jiang-Jiang Tang、Gui-Juan Fan、Fang Dai、De-Jun Ding、Qi Wang、Dong-Liang Lu、Ran-Ran Li、Xiu-Zhuang Li、Li-Mei Hu、Xiao-Ling Jin、Bo Zhou

  DOI：10.1016/j.freeradbiomed.2011.02.028

  日期：2011.5

  Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is

  白藜芦醇作为天然抗氧化剂和癌症化学预防剂是广泛研究的主题。在过去十年中，人们对它的作用机理以及开发出具有比母体化合物更好的抗氧化剂和癌症化学预防活性的类似物产生了极大的兴趣和激动。这项工作表明，共轭键的延长是提高白藜芦醇类似物抗氧化活性的重要策略，包括在均相溶液中的氢原子或电子供电能力以及在非均相介质中的抗溶血活性。更重要的是，与白藜芦醇相比，带有3,4'-二羟基基团的三烯C3作为重要的先导化合物浮出水面，显示出显着提高的抗氧化剂，细胞毒性和诱导细胞凋亡的活性。
• Engineered Chimeric Enzymes as Tools for Drug Discovery:  Generating Reliable Bacterial Screens for the Detection, Discovery, and Assessment of Estrogen Receptor Modulators
  作者：Georgios Skretas、Aggeliki K. Meligova、Carolina Villalonga-Barber、Dimitra J. Mitsiou、Michael N. Alexis、Maria Micha-Screttas、Barry R. Steele、Constantinos G. Screttas、David W. Wood

  DOI：10.1021/ja067754j

  日期：2007.7.1

  Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.