(E)-3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one | 111797-23-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one
• 英文别名: 3,3',4,4',5'-Pentamethoxychalcone；(E)-3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 111797-23-0
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: XCTVYGILKGHJLX-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one 在 双氧水 、 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以74%的产率得到2,3-epoxy-1-(3',4',5'-trimethoxyphenyl)-3-(3'',4''-dimethoxyphenyl)propanone
  参考文献：
  名称：

  Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins

  摘要：

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.028
• 作为产物：
  描述：

  (3,4,5-三甲氧基苯甲酰基)丙二酸二乙酯 在 乙醇 、 硫酸 、 苄基三甲基氢氧化铵 作用下， 生成 (E)-3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one
  参考文献：
  名称：

  Experiments in the Colchicine Field. V. The Thermal and Photochemical Decomposition of Various 2-(β-Phenylethyl)-phenyldiazomethanes and 2-(γ-Phenylpropyl)-phenyldiazomethanes¹

  摘要：

  DOI：

  10.1021/ja01554a043

文献信息

• A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
  作者：Bin Wang、Li-Ren Wang、Lu-Lu Liu、Wei Wang、Ruo-Jun Man、Da-Jun Zheng、Yu-Shan Deng、Yu-Shun Yang、Chen Xu、Hai-Liang Zhu

  DOI：10.1016/j.bioorg.2020.104585

  日期：2021.3

  In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。
• The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1 Expressing Breast Cancer Cells
  作者：Ketan C. Ruparelia、Keti Zeka、Taeeba Ijaz、Dyan N. Ankrett、Nicola E. Wilsher、Paul C. Butler、Hoon L. Tan、Sabahat Lodhi、Avninder S. Bhambra、Gerard A. Potter、Randolph R.J. Arroo、Kenneth J.M. Beresford

  DOI：10.2174/1573406414666180112120134

  日期：2018.5.11

  Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objective: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Result: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and α-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusion: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved.

  背景：尽管许多 P450 在肿瘤和相应正常组织中的表达水平不同，CYP1B1 是少数在肿瘤中显著且一致过表达的 CYP 亚家族之一。研究表明，CYP1B1在肿瘤中具有活性，并且能够代谢结构多样的抗癌药物。因此，以及其在激活前致癌物中的作用，CYP1B1 被视为抗癌药物开发的重要靶点。 目标：基于化学预防剂 DMU-135 合成一系列查尔酮衍生物，并研究它们在表达 CYP1B1 和 CYP1A1 的人乳腺癌细胞系中的抗增殖活性。 方法：通过克来森-施密特缩合反应合成了产率为 43-94%的一系列查尔酮。这些化合物通过 MTT assay 对一组已知 CYP1 表达的乳腺癌细胞系进行了筛选。 结果：许多衍生物在表达 CYP1B1 和 CYP1A1 的人乳腺癌细胞系中显示出有前景的抗增殖活性，同时对没有 CYP 表达的非肿瘤乳腺癌细胞系显示出显著较低的毒性。使用 CYP1抑制剂 acacetin 和 α-naphthoflavone 的实验为这些化合物在生物激活过程中涉及 CYP1 酶提供了支持性证据。 结论：查尔酮作为抗癌药物显示出潜力，有证据表明这些化合物的 CYP1 激活可能参与其中。
• Synthesis and biological evaluation of 3′,4′,5′-trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation
  作者：Yerra Koteswara Rao、Shih-Hua Fang、Yew-Min Tzeng

  DOI：10.1016/j.bmc.2009.10.022

  日期：2009.12

  anti-proliferative compound in the series with IC50 values of 1.8 and 2.2 μM toward liver cancer Hep G2 and colon cancer Colon 205 cell lines, respectively. 2,3,3′,4′,5′-Pentamethoxychalcone (1), 3,3′,4,4′,5,5′-hexamethoxychalcone (3), 2,3′,4,4′,5,5′-hexamethoxychalcone (5), 2-hydroxy-3,3′,4′,5′-tetramethoxychalcone (10), 11 and 14 showed significant anti-proliferation actions in Hep G2 and Colon 205

  合成了一系列23 3'，4'，5'-三甲氧基查耳酮类似物，它们对LPS /IFN-γ处理的巨噬细胞中一氧化氮（NO）的抑制作用，并研究了肿瘤细胞的增殖。4-羟基-3,3'，4'，5'-四甲氧基查尔酮（7），3,4-二羟基-3'，4'，5'-三甲氧基查尔酮（11），3-羟基-3'，4,4 '，5'-四甲氧基查耳酮（14）和3,3'，4'，5'-四甲氧基查耳酮（15）是产生NO最有效的生长抑制剂，IC 50值为0.3、1.5、1.3和0.3分别为μM。肿瘤细胞增殖测定结果表明，几种化合物对不同的癌细胞系表现出有效的抑制活性。查尔酮15是该系列中最有效的抗增殖化合物，对肝癌Hep G2和结肠癌Colon 205细胞系的IC 50值分别为1.8和2.2μM。2,3,3'，4'，5'-五甲氧基查耳酮（1），3,3'，4,4'，5,5'-六甲氧基查耳酮（3），2,3'，4,4'，5， 5'-六甲氧基查耳酮（5），2-羟基-3
• Identification of chalcone analogues as anti-inflammatory agents through the regulation of NF-κB and JNK activation
  作者：Die Zhang、Wenping Wang、Huiping Ou、Jinhua Ning、Yingxun Zhou、Jin Ke、Anguo Hou、Linyun Chen、Peng Li、Yunshu Ma、Wen Bin Jin

  DOI：10.1039/d4md00011k

  日期：——

  To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds was evaluated by screening their inhibitory effects on NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected for further investigation by assessment of their dose-dependent

  为了开发具有改进药物特性的新型抗炎剂，设计并合成了一系列查尔酮类似物。通过筛选这些化合物对 RAW264.7 细胞系中 NO 产生的抑制作用来评估这些化合物的体外抗炎活性。通过评估其对细胞因子（如 TNF-α、IL-1β、IL-6 和 PGE2 释放）的剂量依赖性抑制活性，选择最有前途的化合物3h和3l进行进一步研究。进一步研究还表明3h和3l可通过NF-κB/JNK信号通路显着抑制iNOS和COX-2的表达。此外，化合物3h和3l还可以显着抑制炎症相关基因的mRNA表达。同时， 3小时也可以下调ROS的产生。进行对接模拟以将化合物3h和3l定位到 iNOS 结合位点以预测可能的结合模式。总之，通过计算机快速预测获得的这一系列具有合理药物相似性的查耳酮类似物可以用作有前途的先导候选物。
• Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
  作者：Sylvie Ducki、David Rennison、Meiko Woo、Alexander Kendall、Jérémie Fournier Dit Chabert、Alan T. McGown、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.039

  日期：2009.11

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.