4-hydroxy-3',4',5'-trimethoxychalcone | 104554-34-9

• 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: 4-hydroxy-3',4',5'-trimethoxychalcone
• 英文别名: 3-(4-Hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 104554-34-9
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: AYICHAKPDXZAMD-UHFFFAOYSA-N

物化性质

• 沸点：
  507.3±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3',4',5'-trimethoxychalcone 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.74h， 生成 4-[N¹-(N⁴,N⁹,N¹²-ter-tert-butyloxycarbonyl)-spermine-3-aminopropyloxy]-3',4',5'-trimethoxychalcone
  参考文献：
  名称：

  查尔酮-多胺偶联物作为结直肠癌和前列腺癌化疗中新型载体化药物的合成和生物学评价

  摘要：

  本研究的目的是使用基于多胺的载体合成查尔酮-多胺偶联物，以提高查尔酮核心对癌细胞的生物利用度和选择性。事实上，众所周知，多胺转运系统在肿瘤细胞中被上调。3',4,4',5'-四甲氧基查尔酮被选为母查尔酮，因为它被发现是对各种癌细胞的有效抗增殖剂。使用 4-溴丙氧基-3',4',5'-三甲氧基查尔酮作为关键中间体，获得了一系列五种查尔酮-多胺偶联物。查耳酮核和多胺尾通过胺键融合。发现这些缀合物具有显着的体外对结肠直肠癌（HT-29 和 HCT-116）和前列腺癌（PC-3 和 DU-145）细胞系具有抗增殖作用。最活跃的偶联物（化合物8b) 然后被选择用于进一步的生物学评估，以阐明其抗增殖活性的机制。对细胞周期分布的研究表明，这种结合物可以通过分别阻断 G1 和 G2 期的细胞周期来阻止人类结直肠癌细胞和前列腺癌细胞的增殖。流式细胞术分析揭示了一个亚 G1 峰，这是凋亡细胞群的特征，我们的调

  DOI：

  10.1016/j.ejmech.2021.113586
• 作为产物：
  描述：

  对羟基苯甲醛 在 4-甲基苯磺酸吡啶 、 对甲苯磺酸 、 barium(II) hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 28.33h， 生成 4-hydroxy-3',4',5'-trimethoxychalcone
  参考文献：
  名称：

  查尔酮-多胺偶联物作为结直肠癌和前列腺癌化疗中新型载体化药物的合成和生物学评价

  摘要：

  本研究的目的是使用基于多胺的载体合成查尔酮-多胺偶联物，以提高查尔酮核心对癌细胞的生物利用度和选择性。事实上，众所周知，多胺转运系统在肿瘤细胞中被上调。3',4,4',5'-四甲氧基查尔酮被选为母查尔酮，因为它被发现是对各种癌细胞的有效抗增殖剂。使用 4-溴丙氧基-3',4',5'-三甲氧基查尔酮作为关键中间体，获得了一系列五种查尔酮-多胺偶联物。查耳酮核和多胺尾通过胺键融合。发现这些缀合物具有显着的体外对结肠直肠癌（HT-29 和 HCT-116）和前列腺癌（PC-3 和 DU-145）细胞系具有抗增殖作用。最活跃的偶联物（化合物8b) 然后被选择用于进一步的生物学评估，以阐明其抗增殖活性的机制。对细胞周期分布的研究表明，这种结合物可以通过分别阻断 G1 和 G2 期的细胞周期来阻止人类结直肠癌细胞和前列腺癌细胞的增殖。流式细胞术分析揭示了一个亚 G1 峰，这是凋亡细胞群的特征，我们的调

  DOI：

  10.1016/j.ejmech.2021.113586

文献信息

• <i>N</i>‐methylpiperazinyl and <scp>piperdinylalkyl‐</scp><i>O</i>‐chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation
  作者：Pratibha Sharma、Varinder Singh、Manjinder Singh

  DOI：10.1111/cbdd.14318

  日期：2023.11

  The series of N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfuctional agents against Alzheimer's disease that have been designed, synthesized and then evaluated biologically using in vitro assays for the inhibition of acetylcholinesterase (AChE) activity, AGEs, and free radical formation. The majority of synthesized compounds inhibited AChE & AGEs with additional free radical scavenging activities at nanomolar concentrations. Among these, compound 5k was found to have potent AChE inhibitory activity (IC₅₀ = 11.6 nM), superior than the reference compound donepezil (15.68 nM) along with the good anti‐AGEs and free radical formation effect. Its potency was justified by docking studies that revealed its dual binding characteristic with both catalytic active site and peripheral anionic site of AChE, simultaneously. Furthermore, the in vivo evaluation of 5k against streptozotocin (STZ)‐induced dementia in rats also showed improvement of memory functions (Morris water maze test) in animals. Also, 5k inhibited STZ‐inudced brain AChE activity and oxidative stress which further strengthen the observed in vitro effects. The stability of the ligand‐protein complex was then analyzed using a simulation‐based interaction protocol. The results revealed that these N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives could be considered for potential polyfunctional anti‐Alzheimer's molecules.

  摘要 设计、合成了一系列 N-甲基哌嗪基和哌啶基烷基-O-查尔酮衍生物，并利用体外实验对其抑制乙酰胆碱酯酶（AChE）活性、AGEs 和自由基形成的能力进行了生物评估，将其作为抗老年痴呆症的潜在多药。合成的大多数化合物都能抑制乙酰胆碱酯酶的活性；在纳摩尔浓度下，AGEs 还具有清除自由基的活性。其中，化合物 5k 具有强效 AChE 抑制活性（IC50 = 11.6 nM），优于参考化合物多奈哌齐（15.68 nM），同时还具有良好的抗 AGEs 和自由基形成作用。通过对接研究发现，它同时与 AChE 的催化活性位点和外周阴离子位点具有双重结合特性，从而证明了它的有效性。此外，5k 对链脲佐菌素（STZ）诱导的大鼠痴呆症的体内评估也表明，它能改善动物的记忆功能（莫里斯水迷宫测试）。此外，5k 还能抑制 STZ 引起的脑 AChE 活性和氧化应激，这进一步加强了体外观察到的效果。然后，利用基于模拟的相互作用协议分析了配体-蛋白质复合物的稳定性。结果表明，这些 N-甲基哌嗪基和哌啶基烷基-O-查尔酮衍生物可被视为潜在的多功能抗阿尔茨海默氏症分子。
• Structure−Activity Relationship Studies of Chalcone Leading to 3-Hydroxy-4,3′,4′,5′-tetramethoxychalcone and Its Analogues as Potent Nuclear Factor κB Inhibitors and Their Anticancer Activities
  作者：Balasubramanian Srinivasan、Thomas E. Johnson、Rahul Lad、Chengguo Xing

  DOI：10.1021/jm901278z

  日期：2009.11.26

  Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappa B) activation. The structures of chalcone-based NF-kappa B inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappa B inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappa B inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappa B inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappa B inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappa B inhibitory activities, suggesting that suppressing NF-kappa B activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.
• Examination of growth inhibitory properties of synthetic chalcones for which antibacterial activity was predicted
  作者：Daniela Batovska、Stoyan Parushev、Bistra Stamboliyska、Iva Tsvetkova、Mariana Ninova、Hristo Najdenski

  DOI：10.1016/j.ejmech.2008.05.010

  日期：2009.5

  A large series of chalcones were synthesized and studied against Staphylococcus aureus and Escherichia coli. Chalcones were either unsubstituted in ring A or possessed 4-chloro or 3',4',5'-trimethoxy groups. Their other ring B was variously substituted. It was found that the antistaphylococcal activity of chalcones was related to the energy difference between the two highest occupied molecular orbitals (HOMO and HOMO-1). Presence of hydroxyl group in ring B was not a determinant factor for the anti-staphylococcal activity, but the lipophilicity of ring A of the hydroxyl chalcones was of importance. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines
  作者：Ashish Ranjan Dwivedi、Vijay Kumar、Harmeet Kaur、Naveen Kumar、Ravi Prakash Yadav、Ramarao Poduri、Somesh Baranwal、Vinod Kumar

  DOI：10.1016/j.bmcl.2020.127468

  日期：2020.10

  A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 mu M, 4.78 mu M and 4.23 mu M, HK-10 showed IC50 values of 0.81 mu M, 5.89 mu M, 4.96 mu M and HK-13 showed IC50 values 3.24 mu M, 4.93 mu M and 4.73 mu M against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 mu M against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development.
• Identification of 3′,4′,5′-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells
  作者：Chih-Ho Lai、Yerra Koteswara Rao、Shih-Hua Fang、Yu-Ting Sing、Yew-Min Tzeng

  DOI：10.1016/j.bmcl.2010.07.094

  日期：2010.9

  Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8. (c) 2010 Elsevier Ltd. All rights reserved.