bisdemethoxycurcumin | 98885-87-1

• 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: bisdemethoxycurcumin
• 英文别名: BDMC；(1E,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
• CAS: 98885-87-1
• 化学式: C₁₉H₁₆O₄
• 分子量: 308.334
• InChiKey: YXAKCQIIROBKOP-LGKPSKQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.76
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  bisdemethoxycurcumin 在 盐酸羟胺 、 溶剂黄146 作用下， 以87%的产率得到3,5-bis(4-hydroxystyryl)isoxazole
  参考文献：
  名称：

  姜黄素衍生的3,5-双（苯乙烯基）异恶唑-机械化学合成和抗氧化活性

  摘要：

  姜黄素衍生的3,5-双（苯乙烯基）异恶唑的机械化学合成及其抗氧化活性已有报道。 姜黄素衍生的3,5-双（苯乙烯基）异恶唑（4a-g）的机械化学合成及其抗氧化活性已有报道。

  DOI：

  10.1007/s12039-016-1119-8
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 bisdemethoxycurcumin
  参考文献：
  名称：

  Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

  摘要：

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.073

文献信息

• Mining Plants for Bacterial Quorum Sensing Modulators
  作者：Shimrit David、Aviad Mandabi、Shaked Uzi、Asaph Aharoni、Michael M. Meijler

  DOI：10.1021/acschembio.7b00859

  日期：2018.1.19

  uses quorum sensing (QS) in order to regulate the transfer of DNA into the host plant genome, and this results in the induction of crown gall tumors. The deleterious results of these infections are widespread and affect many species of fruit and crops. In order to further our understanding of this process and to provide potential solutions, we evaluated a library of 3800 natural products from plant

  细菌植物病原体根癌农杆菌使用群体感应（QS）来调节DNA向宿主植物基因组中的转移，从而导致冠状胆囊肿瘤的诱导。这些感染的有害结果广泛存在，并影响许多种类的水果和农作物。为了进一步了解该过程并提供可能的解决方案，我们评估了一个来自植物的3800种天然产物的库，并确定了能够强烈调节植物与细菌相互作用的有效化合物。
• Synthesis, characterization, cytotoxic activity of half-sandwich rhodium(III), and iridium(III) complexes with curcuminoids
  作者：Wei Su、Xiaohui Wang、Xiaolin Lei、Qi Xiao、Shan Huang、Peiyuan Li

  DOI：10.1016/j.jorganchem.2017.01.028

  日期：2017.3

  A series of organometallic rhodium and iridium complexes with curcuminoid ligands (1–14) have been synthesized and characterized by NMR, IR, elemental analysis, and HR-ESI-mass spectrometry. The molecular structure of complex 9 has been characterized by X-ray crystallography. The in vitro activity of all the compounds has been evaluated against the HepG2, HeLa human cancer cell lines and HEK-293T human

  一系列有机金属铑和铱配合物类姜黄素配体（的1 - 14）已经被合成和表征通过NMR，IR，元素分析，和HR-ESI-MS分析。配合物9的分子结构已经通过X射线晶体学表征。在体外的所有化合物的活性已靠着HepG2细胞，HELA人癌细胞系和HEK-293T人类健康的细胞系进行了评价。铑配合物6表现出优异的抗癌活性和对癌细胞系的有希望的选择性。此外，电泳迁移率谱研究紧随6与DNA的相互作用。
• Cocrystallization of Curcuminoids with Hydroxybenzenes Pyrogallol and Hydroxyquinol: Investigations of Binary Thermal Phase Behaviors
  作者：Steffi Wünsche、Andreas Seidel-Morgenstern、Heike Lorenz

  DOI：10.1021/acs.cgd.2c00123

  日期：2022.5.4

  The binary thermal phase behaviors of the curcuminoids (CURDs) curcumin (CUR), demethoxycurcumin (DMC), and bis(demethoxy)curcumin (BDMC) with either pyrogallol (PYR) and hydroxyquinol (HYQ) as potential cocrystal formers were investigated. Earlier, it was reported that CUR and BDMC form cocrystals in a 1:1 stoichiometric ratio with the aforementioned coformers. Here, we report for the first time cocrystallization experiments of DMC. Two different cocrystallization techniques, namely, liquid-assisted grinding and cocrystallization from the melt phase, were applied. Analyses of the cocrystallization outcomes were performed using powder X-ray diffraction and differential scanning calorimetry (DSC). A cocrystal phase of DMC with one of the two trihydroxybenzenes could not be found, but a simple eutectic behavior was proven. Binary phase diagrams of all six systems were constructed from DSC measurements revealing distinct thermal behaviors: The CUR cocrystals both melt congruently, while the BDMC cocrystals show an incongruent melting behavior. Together with the eutectic DMC systems, we found three different types of binary phase behaviors for the CURD systems, which can serve as a basis for future crystallization-based purification of structurally similar CURDs.

  本文研究了姜黄素（CUR）、去甲氧基姜黄素（DMC）和双（去甲氧基）姜黄素（BDMC）与焦性没食子酸（PYR）和羟基喹啉（HYQ）作为潜在共晶形成剂的二元热相行为。此前有报道称，CUR和BDMC与上述共晶形成剂以1:1的化学计量比形成共晶。本文首次报道了DMC的共晶实验。共晶实验采用了两种不同的技术，即液相辅助研磨和熔融相共晶。共晶结果的分析采用粉末X射线衍射和差示扫描量热法（DSC）。虽然未能发现DMC与两种三羟基苯之一形成的共晶相，但证明了简单的共熔行为。DSC测量构建了所有六个系统的二元相图，揭示了不同的热行为：CUR共晶同时熔融，而BDMC共晶则表现出不共融的熔融行为。与共熔DMC系统一起，我们发现了CURD系统的三种不同类型的二元相行为，这可以作为未来基于结晶的类似结构CURD纯化的基础。
• 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.
• Antibacterial activity of 3,3′-dihydroxycurcumin (DHC) is associated with membrane perturbation
  作者：Carlos R. Polaquini、Luana G. Morão、Ana C. Nazaré、Guilherme S. Torrezan、Guilherme Dilarri、Lúcia B. Cavalca、Débora L. Campos、Isabel C. Silva、Jessé A. Pereira、Dirk-Jan Scheffers、Cristiane Duque、Fernando R. Pavan、Henrique Ferreira、Luis O. Regasini

  DOI：10.1016/j.bioorg.2019.103031

  日期：2019.9

  Curcumin is a plant diphenylheptanoid and has been investigated for its antibacterial activity. However, the therapeutic uses of this compound are limited due to its chemical instability. In this work, we evaluated the antimicrobial activity of diphenylheptanoids derived from curcumin against Gram-positive and Gram-negative bacteria, and also against Mycobacterium tuberculosis in terms of MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values. 3,3'-Dihydroxycurcumin (DHC) displayed activity against Enterococcus faecalis, Staphylococcus aureus and M. tuberculosis, demonstrating MIC values of 78 and 156 mu g/mL. In addition, DHC was more stable than curcumin in acetate buffer (pH 5.0) and phosphate buffer (pH 7.4) for 24 h at 37 degrees C. We proposed that membrane and the cell division protein FtsZ could be the targets for DHC due to that fact that curcumin exhibits this mode of antibacterial action. Fluorescence microscopy of Bacillus subtilis stained with SYTO9 and propidium iodide fluorophores indicated that DHC has the ability to perturb the bacterial membrane. On the other hand, DHC showed a weak inhibition of the GTPase activity of B. subtilis FtsZ. Toxicity assay using human cells indicated that DHC has moderate capacity to reduce viability of liver cells (HepG2 line) and lung cells (MRC-5 and A549 lines) when compared with doxorubicin. Alkaline comet assay indicated that DHC was not able to induce DNA damage in A549 cell line. These results indicated that DHC is promising compound with antibacterial and antitubercular activities.