dimethoxycurcumin

• 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: dimethoxycurcumin
• 英文别名: (1E,6E)-1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
• 化学式: C₂₃H₂₄O₆
• 分子量: 396.44
• InChiKey: ZMGUKFHHNQMKJI-URFDALOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethoxycurcumin 在 盐酸 、 4-二甲氨基吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 13.0h， 生成 2,2-bis((E)-3-(3,4-dimethoxyphenyl)acryloyl)propane-1,3-diylbis(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate)
  参考文献：
  名称：

  Synthesis, Anticancer Activity, and Preliminary Pharmacokinetic Evaluation of 4,4-Disubstituted Curcuminoid 2,2-bis(Hydroxymethyl)Propionate Derivatives

  摘要：

  化合物1是一种姜黄双-O-2,2-双(羟甲基)丙酸酯，对MDA-MB-231细胞显示出显著的体外和体内抑制活性，比姜黄的效力高出八到十倍。在这里，我们通过在1的中心1,3-二酮基团的α-位置（C-4位置）上修饰极性或非极性功能团，制备了一系列4,4-二取代姜黄素2,2-双(羟甲基)丙酸酯衍生物，并评估了它们的抗癌活性。基于它们对MDA-MB-231和HCT-116细胞系的抗增殖效应，建立了化合物1衍生物的结构-活性关系，重点关注C-4位置的功能团。化合物2-6分别是4,4-二甲基化、4,4-二乙基化、4,4-二苄基化、4,4-二丙炔基化和4,4-二烯丙基化的化合物1。化合物2m-6m分别是化合物2-6的酯水解产物，已合成并评估了它们的抗癌活性。在所有化合物1衍生物中，化合物2因其对HCT-116的有希望的体内抗增殖活性（IC50 = 3.10 ± 0.29 μM）以及其酯水解产物2m（IC50 = 2.17 ± 0.16 μM）而被确定为结肠癌的潜在化疗药物。化合物2的初步药代动力学评估表明，2和2m是体内疗效的主要贡献者。化合物2在使用HCT-116结肠肿瘤裸鼠移植模型进行的动物研究中进一步评估。结果显示，分别在50、100和150 mg/kg剂量下，导致肿瘤体积减少27％、45％和60％的剂量依赖性疗效。2的建立的结构-活性关系和药代动力学结果是未来开发4,4-二取代姜黄素2,2-双(羟甲基)丙酸酯衍生物作为抗癌药物候选药物的指导。

  DOI：

  10.3390/molecules25030479
• 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 dimethoxycurcumin
  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

• Design, synthesis, and evaluation of curcumin analogues as potential inhibitors of bacterial sialidase
  作者：Bo Ram Kim、Ji-Young Park、Hyung Jae Jeong、Hyung-Jun Kwon、Su-Jin Park、In-Chul Lee、Young Bae Ryu、Woo Song Lee

  DOI：10.1080/14756366.2018.1488695

  日期：2018.1.1

  Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis

  唾液酸酶是关键的毒力因子，可从宿主细胞表面聚糖中去除唾液酸，从而暴露促进细菌粘附和定植的受体。在这项研究中，我们开发了治疗由肺炎链球菌 Nan A 引起的细菌感染的潜在药物，该药物使用姜黄和姜黄素类似物抑制细菌唾液酸酶。还描述了设计、综合和结构分析关系（SAR）研究。对合成衍生物的评估表明，化合物 5e 是肺炎链球菌唾液酸酶最有效的抑制剂（IC50 = 0.2 ± 0.1 µM）。该化合物的抑制活性比姜黄素提高了 3.0 倍，并表现出竞争性抑制作用。这些结果值得进一步研究证实抗肺炎球菌活性 5e 并表明姜黄素衍生物可能用于治疗细菌感染引起的脓毒症。
• A New Family of Homoleptic Copper Complexes of Curcuminoids: Synthesis, Characterization and Biological Properties
  作者：William Meza-Morales、Juan Machado-Rodriguez、Yair Alvarez-Ricardo、Marco Obregón-Mendoza、Antonio Nieto-Camacho、Rubén. Toscano、Manuel Soriano-García、Julia Cassani、Raúl Enríquez

  DOI：10.3390/molecules24050910

  日期：——

  in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR)

  我们在此报道了五种新的类姜黄素均配铜配合物的合成和晶体结构。类姜黄素均配复合结构报道的稀缺归因于此类衍生物缺乏结晶度，因此，通过单晶 X 射线衍射对其进行表征的情况很少。通过酯化或醚化抑制酚类相互作用的配体设计显着增加了类姜黄素均配金属配合物的已知晶体结构的数量，揭示了更有利的结晶度。目前的新型铜配合物的晶体结构显示出具有方形平面几何形状的四重配位。当从 DMF 中结晶时，发现了 DiBncOC-Cu 的两种多晶型物。使用红外辐射（IR）、核磁共振（NMR）、电子顺磁共振（EPR）和单晶X射线衍射（SCXRD）对这些新配合物进行了表征，并对所得配合物的抗氧化和细胞毒活性进行了表征。被评价。
• Kinetics of curcumin oxidation by 2,2-diphenyl-1-picrylhydrazyl (DPPH˙): an interesting case of separated coupled proton–electron transfer
  作者：Mario C. Foti、Adriana Slavova-Kazakova、Concetta Rocco、Vessela D. Kancheva

  DOI：10.1039/c6ob01439a

  日期：——

  The decay of dpph˙ in absolute ethanol at 25 °C and in the presence of curcumin (1), 4-methylcurcumin (3), 4,4-dimethylcurcumin (4) or curcumin 4′-methyl ether (5) follows bi-exponential kinetics. These unusual reaction kinetics are compatible with a two-step process in which an intermediate accumulates in a reversible first step followed by an irreversible process. As in other similar cases (Foti

  在25°C和无姜黄素（1），4-甲基姜黄素（3），4,4-二甲基姜黄素（4）或姜黄素4'-甲基醚（5）的存在下于25°C的无水乙醇中dpph The的衰减指数动力学。这些异常的反应动力学与两步过程兼容，在该过程中，中间体在可逆的第一步中积累，然后在不可逆的过程中积累。如在其它类似的情况下（福蒂等人，有机化学快报，2011，13，4826-4829），我们已经假设，中间是一个π堆叠复杂，一个姜黄素阴离子之间形成（在的情况下1，3和5该烯醇化物阴离子）和的苦基部分DPPH ˙，其中来自（烯醇）阴离子帧内复杂的电子转移发生。通过比较姜黄素4'，4''-二甲醚（2）（无酚羟基），（5）（一种酚羟基）和（1）（两种酚羟基）的动力学，我们推论出电子转移过程必须同时进行质子从酚醛OH到本体溶剂的转移（分离的质子-电子耦合转移）。速率常数ķ α为正向反应2，5和1与DPPHin实际上明显取决于酚OH的数量，分别为〜0、7
• Curcuminoid-derived 3,5-bis(styryl)isoxazoles - Mechanochemical synthesis and antioxidant activity
  作者：DAISY R SHERIN、KALLIKAT N RAJASEKHARAN

  DOI：10.1007/s12039-016-1119-8

  日期：2016.8

  Mechanochemical synthesis of curcuminoid-derived 3,5-bis(styryl)isoxazoles and their antioxidant activities are reported. Mechanochemical synthesis of curcuminoid-derived 3,5-bis(styryl)isoxazoles (4a-g) and their antioxidant activities are reported.

  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。
• 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。