3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)pr op-2-en-1-one | 524945-10-6

• 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: 3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)pr op-2-en-1-one
• 英文别名: 3-hydroxy-3',4,4',5'-tetramethoxychalcone；3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 524945-10-6
• 化学式: C₁₉H₂₀O₆
• 分子量: 344.364
• InChiKey: IKMOZUDCUBMIRL-UHFFFAOYSA-N

物化性质

• 沸点：
  555.2±50.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)pr op-2-en-1-one 在 ammonium acetate 、 锌 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以75%的产率得到3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)propan-1-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm901278z
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.25h， 生成 3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)pr op-2-en-1-one
  参考文献：
  名称：

  新的丁二烯衍生物作为微管蛋白聚合抑制剂的合成与评价。

  摘要：

  合成了一系列新的丁二烯衍生物，并被评估为微管蛋白聚合抑制剂，用于治疗癌症。最佳的丁二烯衍生物9a对五种人类癌细胞系的IC50值显示为0.056-0.089μM。本文包括抗增殖活性的机理研究，包括微管蛋白聚合测定，癌细胞形态变化检查，细胞周期停滞分析和凋亡测定。

  DOI：

  10.1016/j.bmc.2017.03.066

文献信息

• Synthesis and biological evaluation of novel chalcone derivatives as a new class of microtubule destabilizing agents
  作者：Xiaochao Huang、Rizhen Huang、Lingxue Li、Shaohua Gou、Hengshan Wang

  DOI：10.1016/j.ejmech.2017.03.031

  日期：2017.5

  A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50

  设计并合成了一系列新颖的查耳酮衍生物作为潜在的抗肿瘤剂。通过1 H NMR，13 C NMR和HR-MS确认目标分子的结构，并使用MTT分析评估其体外抗增殖活性。其中，化合物12k对测试肿瘤细胞系（包括多药耐药性人类癌症系）表现出强效活性，IC50值为3.75至8.42μM。此外，发现化合物12k通过线粒体途径诱导NCI-H460细胞凋亡，包括ROS水平升高，线粒体膜电位丧失，细胞色素c释放，Bcl-2下调，上调Bax的激活，分别激活caspase-9和caspase-3。此外，细胞周期分析表明12k有效地导致细胞周期停滞在G2 / M期。微管蛋白聚合测定的结果表明，12k可以抑制微管蛋白的体外聚合。此外，分子对接研究表明12k可以与微管蛋白的秋水仙碱位点结合。
• Engineering Enzyme‐Cleavable Oligonucleotides by Automated Solid‐Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers
  作者：Cheng Jin、Afaf H. EI‐Sagheer、Siqi Li、Katherine A. Vallis、Weihong Tan、Tom Brown

  DOI：10.1002/anie.202114016

  日期：2022.3.21

  automated synthesis of enzyme-cleavable oligonucleotides. The enzymatic cleavage of Val-Ala-02 by cathepsin B is efficient in the context of single-stranded DNA, but is sterically hindered by double-stranded DNA and short hairpin loops. The design of Val-Ala-Chalcone allows the construction of oligonucleotide–drug conjugates which release their small-molecule payload after enzymatic cleavage.

  组织蛋白酶 B 敏感的二肽亚磷酰胺被开发用于自动合成酶可切割的寡核苷酸。组织蛋白酶 B 对 Val-Ala-02 的酶促切割在单链 DNA 的情况下是有效的，但受到双链 DNA 和短发夹环的空间阻碍。Val-Ala-Chalcone 的设计允许构建寡核苷酸-药物偶联物，这些偶联物在酶切割后释放其小分子有效载荷。
• 一种以新型NF-κB抑制剂为配体的铂(IV)前药及其制备方法和应用
  申请人：淮阴工学院

  公开号：CN117624250A

  公开（公告）日：2024-03-01

  本发明属于药物化学技术领域，具体公开了一种以新型NF‑κB抑制剂为配体的铂(IV)前药及其制备方法和应用，本发明将一种新型NF‑κB抑制剂引入铂(IV)配合物轴向位置，设计、合成了一类具有靶向性强、疗效高和毒性低的新型铂(IV)类抗肿瘤药物；本发明公开的类铂(IV)配合物具有良好的抗肺癌活性，且对人正常肝细胞LO2细胞的毒性较低。此外，该前药对顺铂耐药细胞A549/CDDP表现出了良好的抑制作用。体外研究结果表明，该类铂(IV)前药具有潜在靶向性治疗肺癌的用途。
• Dual-functional conjugates improving cancer immunochemotherapy by inhibiting tubulin polymerization and indoleamine-2,3-dioxygenase
  作者：Shixian Hua、Feihong Chen、Xinyi Wang、Shaohua Gou

  DOI：10.1016/j.ejmech.2020.112041

  日期：2020.3

  A series of novel conjugates comprising tublin and IDO inhibitors were designed, synthesized and evaluated for their antiproliferative activity. Among them, HI5, composed of combretastatin A-4 (CA-4) and (D)-1-methyltryptophan (D -MT) by a linker, exhibited the most potent antitumor activity, in particular with higher IC50 value (0.07 mu M) than CA-4 (0.21 mu M) against HeLa cancer cell line. Mechanism studies indicated that HIS can inhibit tubulin polymerization and cell migration, cause G2/M phase arrest, concurrent induce apoptosis via the mitochondrial dependent apoptosis pathway and cause reactive oxidative stress generation in HeLa cells. Furthermore, HIS can inhibit IDO expression and decrease kynurenine production, leading to stimulating T cells activation and proliferation to enhance antitumor immunity in vitro. Interestingly, HIS can effectively limit the tumor growth in the HeLa xenograft mice models without causing significant loss of body weight. Consequently, such a conjugation can be a potent and safe immunochemotherapeutic method for improving cancer therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.
• A convenient synthesis of cis-restricted combretastatin analogues with pyrazole and isoxazole cores
  作者：Dmitry V. Tsyganov、Marina N. Semenova、Leonid D. Konyushkin、Vladimir I. Ushkarov、Mikhail M. Raihstat、Victor V. Semenov

  DOI：10.1016/j.mencom.2019.03.015

  日期：2019.3

  A series of combretastatin analogues, diarylpyrazoles and diarylisoxazoles, have been synthesized and evaluated for their antimitotic tubulin-binding activity using the phenotypic sea urchin (Paracentrotus lividus) embryo assay. One pyrazole analogue and four isoxazole analogues have been identified as potent antimitotic agents comparable with combretastatins A-2 and A-4, with the lowest observable effective concentration of 1-10 nmol dm(-3) for cleavage alteration of the test embryos.