(E)-1-(2,4-dihydroxyphenyl)-3-(m-tolyl)prop-2-en-1-one | 36574-87-5

• 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)-1-(2,4-dihydroxyphenyl)-3-(m-tolyl)prop-2-en-1-one
• 英文别名: (E)-1-(2,4-dihydroxyphenyl)-3-(3-methylphenyl)prop-2-en-1-one
• CAS: 36574-87-5
• 化学式: C₁₆H₁₄O₃
• 分子量: 254.285
• InChiKey: WZGZRINZQCBMBT-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (E)-1-(2,4-dihydroxyphenyl)-3-(m-tolyl)prop-2-en-1-one 在 盐酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 26.0h， 生成 (2E)-1-(2, 4-dihydroxyphenyl)-3-(4-methylphenyl)prop-2-en-1-one
  参考文献：
  名称：

  一些吡唑衍生物的合成及其与P-糖蛋白的亲和力结合的初步研究。

  摘要：

  合成了一系列取代的吡唑啉，并通过直接结合至包含ATP结合位点和调节剂相互作用区的纯化蛋白结构域，评估了它们的抗癌活性以及抑制P-糖蛋白介导的多药耐药性的能力。已经发现化合物2a和e以更大的亲和力与P-糖蛋白结合。

  DOI：

  10.1016/j.bmcl.2005.05.067
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 盐酸 、 barium dihydroxide 、 4-甲基苯磺酸吡啶 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 (E)-1-(2,4-dihydroxyphenyl)-3-(m-tolyl)prop-2-en-1-one
  参考文献：
  名称：

  一些吡唑衍生物的合成及其与P-糖蛋白的亲和力结合的初步研究。

  摘要：

  合成了一系列取代的吡唑啉，并通过直接结合至包含ATP结合位点和调节剂相互作用区的纯化蛋白结构域，评估了它们的抗癌活性以及抑制P-糖蛋白介导的多药耐药性的能力。已经发现化合物2a和e以更大的亲和力与P-糖蛋白结合。

  DOI：

  10.1016/j.bmcl.2005.05.067

文献信息

• On the role of synthesized hydroxylated chalcones as dual functional amyloid-β aggregation and ferroptosis inhibitors for potential treatment of Alzheimer's disease
  作者：Lin Cong、Xiyu Dong、Yan Wang、Yulin Deng、Bo Li、Rongji Dai

  DOI：10.1016/j.ejmech.2019.01.039

  日期：2019.3

  In addition to amyloid cascade hypothesis, ferroptosis – a recently identified cell death pathway associated with the accumulation of lipid hydroperoxides – was hypothesized as one of the main forms of cell death in Alzheimer's disease. Herein, a series of hydroxylated chalcones were designed and synthesized as dual-functional inhibitors to inhibit amyloid-β peptide (Aβ) aggregation as well as ferroptosis

  除淀粉样蛋白级联假说外，铁蛋白增生症（一种最近发现的与脂质过氧化氢的积累有关的细胞死亡途径）被认为是阿尔茨海默氏病的主要细胞死亡形式之一。本文中，设计并合成了一系列羟基化的查耳酮作为双功能抑制剂，以同时抑制淀粉样β肽（Aβ）的聚集以及肥大症。硫黄素-T测定表明三羟基查耳酮更好地抑制了Aβ聚集。在人神经母细胞瘤SH-SY5Y细胞中，具有三个羟基取代基的细胞保护查耳酮14a-c对Aβ1-42聚集诱导的毒性表现出显着的神经保护作用。此外，查尔孔涅斯14a-c被发现是通过使用过氧化氢-酶解毒的Gpx4任一药理学抑制（感应ferroptosis的良好抑制剂1S，3R）或-RSL4胱氨酸/谷氨酸反向转运蛋白系统X Ç -抑制erastin通过脂质过氧化抑制机制。三羟基查尔酮14a还能够完全破坏SH-SY5Y细胞中Aβ1-42聚集诱导的脂质过氧化反应，表明它们可以减少与氧化应激有关的神经毒性。化合物14
• Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines
  作者：Shailima Rampogu、Seong Min Kim、Baji Shaik、Gihwan Lee、Ju Hyun Kim、Gon Sup Kim、Keun Woo Lee、Myeong Ok Kim

  DOI：10.3389/fonc.2021.712824

  日期：——

  Breast cancer is one of the major causes of mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast cancer to which currently there are no reported or approved drugs.

  To find effective cancer therapeutics, three compounds were computationally designed tweaking the structure of natural compound butein. These compounds were synthesized and evaluated for their anticancer property in MCF-7 and MDA-MB-231 cell lines targeting DDX3. The in silico molecular docking studies have shown that the compounds have occupied the binding site of the human DDX3 target. Furthermore, to investigate the cell viability effect of 3a, 3b, and 3c on MCF-7 and MDA-MB-231 cell lines, the cell lines were treated with different concentrations of compounds for 24 and 48 h and measured using MTT assay.

  The cell viability results showed that the have induced dose dependent suppression of DDX3 expression. Additionally, 3b and 3c have reduced the expression of DDX3 in MCF-7 and MDA-MD-231 cell lines. 3b or 3c treated cell lines increased apoptotic protein expression. Both the compounds have induced the apoptotic cell death by elevated levels of cleaved PARP and cleaved caspase 3 and repression of the anti-apoptosis protein BCL-xL. Additionally, they have demonstrated the G2/M phase cell cycle arrest in both the cell lines. Additionally, 3c decreased PI3K and AKT levels.

  Our results shed light on the anticancer ability of the designed compounds. These compounds can be employed as chemical spaces to design new prospective drug candidates. Additionally, our computational method can be adapted to design new chemical scaffolds as plausible inhibitors.

  背景：乳腺癌是全球妇女死亡的主要原因之一。 DDX3已经成为几种癌症的潜在靶点，包括目前没有报道或批准的乳腺癌药物。 方法：为了寻找有效的癌症治疗药物，通过计算设计了三种化合物，调整了天然化合物butein的结构。这些化合物在MCF-7和MDA-MB-231细胞系中合成并评估其针对DDX3的抗癌特性。计算分子对接研究表明，这些化合物占据了人类DDX3靶点的结合位点。此外，为了研究化合物3a、3b和3c对MCF-7和MDA-MB-231细胞系的细胞存活率影响，细胞系被不同浓度的化合物处理24和48小时，并使用MTT测定法测量。 结果：细胞存活率结果表明，这些化合物诱导了剂量依赖性抑制DDX3表达。此外，3b和3c减少了MCF-7和MDA-MD-231细胞系中DDX3的表达。3b或3c处理的细胞系增加了凋亡蛋白的表达。这两种化合物通过增加剪切PARP和剪切caspase 3的水平以及抑制抗凋亡蛋白BCL-xL诱导了凋亡细胞死亡。此外，它们在两种细胞系中诱导了G2/M期细胞周期阻滞。此外，3c降低了PI3K和AKT水平。 结论：我们的结果揭示了设计化合物的抗癌能力。这些化合物可以被用作设计新的潜在药物候选者的化学空间。此外，我们的计算方法可以被调整为设计新的化学支架作为可能的抑制剂。
• Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives
  作者：Fedele Manna、Franco Chimenti、Adriana Bolasco、Daniela Secci、Bruna Bizzarri、Olivia Befani、Paola Turini、Bruno Mondovı̀、Stefano Alcaro、Andrea Tafi

  DOI：10.1016/s0960-894x(02)00699-6

  日期：2002.12

  A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1-6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low 150 values of particular interest. In particular 1-acetyl-3-(2,4-dihydroxyphenyl)-5-(3-methylphenyl)-4,5-dihydro-(1H)-pyrazole 6 showed to be a potent monoamine oxidase inhibitor with a K-i of about 10(-8) M. Further insights in the theoretical evaluation of the possible interactions between the compounds and monoamine oxidase B have been developed through a computational approach. (C) 2002 Elsevier Science Ltd. All rights reserved.