(1E,4Z,6E)-1,7-bis(3,4-dihydroxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one

• 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: (1E,4Z,6E)-1,7-bis(3,4-dihydroxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
• 英文别名: tetrahydroxy curcumin；didemethylcurcumin；(1E,4Z,6E)-1,7-bis(3,4-dihydroxyphenyl)-5-hydroxy-hepta-1,4,6-trien-3-one
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: MQHBAUYEIFLTRU-XVVYLEPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  姜黄素 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 以55%的产率得到(1E,4Z,6E)-1,7-bis(3,4-dihydroxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
  参考文献：
  名称：

  姜黄素单酮衍生物对耐氟康唑的假丝酵母菌的合成及协同抗真菌作用。

  摘要：

  合成了二十三种姜黄素单酮衍生物，以研究与氟康唑对耐氟康唑的念珠菌的协同作用。在体外测定了抗真菌增效剂氟康唑的最低抑菌浓度（MIC 80）和分数抑菌浓度指数（FICI）对耐氟康唑的白色念珠菌，热带念珠菌和克鲁氏梭菌的抑制作用。这些化合物中的大多数对热带念珠菌表现出良好的协同活性。其中，化合物9显示出对念珠菌的显着协同活性。spp。特区也进行了讨论。特别地，细胞生长测试显示，1μgml -1氟康唑和64μgml -1或128μgml -1化合物9的组合显示出对热带假丝酵母最有效的杀真菌作用。协同作用可能与细胞内ATP含量和细胞膜通透性的变化有关。我们的结果为这些化合物作为氟康唑耐药念珠菌病的治疗方法的潜在线​​索提供了未来评估和开发的基础。

  DOI：

  10.1039/c6md00649c

文献信息

• Modulation of proteasome activity by curcumin and didemethylcurcumin
  作者：Tapan K. Khan、Youngki You、Thomas J. Nelson、Subrata Kundu、Saroj K. Pramanik、Joydip Das

  DOI：10.1080/07391102.2021.1911853

  日期：2022.11.24

  multiple signaling pathways. Curcumin shows anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties. Recent research suggests that the therapeutic efficacy of curcumin may be due to its activity as a potent inhibitor of the proteasome. Using in vitro cell culture and molecular docking methods, here we show that both curcumin and its synthetic polyphenolic derivative (didemethylcurcumin

  摘要 通过药理学干预和分子生物学工具调节蛋白酶体功能是癌症生物学和神经退行性疾病研究的一个活跃领域。姜黄素（二阿魏酰甲烷）是一种天然存在的多酚，可影响多种信号通路。姜黄素具有抗炎、抗氧化、抗血管生成或抗细胞凋亡的特性。最近的研究表明，姜黄素的治疗功效可能是由于其作为蛋白酶体有效抑制剂的活性。使用体外细胞培养和分子对接方法，我们在这里表明姜黄素及其合成多酚衍生物（二甲基姜黄素，CUIII）以双相方式调节蛋白酶体活性。姜黄素和 CUIII 在纳摩尔浓度下增加蛋白酶体活性，但在微摩尔浓度下抑制蛋白酶体活性。姜黄素在增加纳摩尔浓度的蛋白酶体相对活性方面比 CUIII 更有效。此外，姜黄素在抑制微摩尔浓度的蛋白酶体活性方面比 CUIII 更有效。估计姜黄素和二甲基姜黄素与 20S 蛋白酶体催化亚基结合的对接模拟K d值分别为 0.0054 µM 和 1.3167 µM。与 CUIII 相比，这些值与
• Cinnamoyl Compounds as Simple Molecules that Inhibit p300 Histone Acetyltransferase
  作者：Roberta Costi、Roberto Di Santo、Marino Artico、Gaetano Miele、Paola Valentini、Ettore Novellino、Anna Cereseto

  DOI：10.1021/jm060943s

  日期：2007.4.1

  vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized

  设计，合成肉桂醛化合物1a-c和2a-d作为p300抑制剂并进行体外测试。在不同程度上，所有被测试的化合物均被证明能使p300失活，特别是衍生物2c是活性最高的抑制剂，与其他组蛋白乙酰转移酶相比，p300也显示出高特异性。最值得注意的是，2c在哺乳动物细胞中显示出抗乙酰酶活性。这些化合物代表了一类新的p300合成抑制剂，其化学结构简单。
• [EN] NOVEL DERIVATIVES OF CURCUMINOIDS AND USE THEREOF AS AN ANTICANCER AGENT<br/>[FR] NOUVEAUX DÉRIVÉS DE CURCUMINOÏDES ET LEUR UTILISATION COMME AGENT ANTICANCÉREUX
  申请人：UNIV CHINA MEDICAL

  公开号：WO2017218219A1

  公开（公告）日：2017-12-21

  A series of novel bis(hydroxymethyl) alkanoate derivatives of curcuminoids were designed, and synthesized, which show anticancer activity, and in particular to breast cancer, colon cancer, and prostate cancer.

  一系列新型的双(羟甲基)烷基酸酯类姜黄素衍生物被设计和合成，表现出抗癌活性，特别是对乳腺癌、结肠癌和前列腺癌。
• THERAPEUTIC CURCUMIN DERIVATIVES
  申请人：STC.UNM

  公开号：US20150011494A1

  公开（公告）日：2015-01-08

  Curcumin analogues and methods are provided for treatment of disease.

  提供了类姜黄素及其方法，用于治疗疾病。
• Geometrically and Conformationally Restrained Cinnamoyl Compounds as Inhibitors of HIV-1 Integrase:  Synthesis, Biological Evaluation, and Molecular Modeling
  作者：Marino Artico、Roberto Di Santo、Roberta Costi、Ettore Novellino、Giovanni Greco、Silvio Massa、Enzo Tramontano、Maria E. Marongiu、Antonella De Montis、Paolo La Colla

  DOI：10.1021/jm9707232

  日期：1998.10.1

  Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2,4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1,3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an "accessory" region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.