(Z)-2-(3-chlorobenzylidene)-4,6-dihydroxybenzofuran-3(2H)-one | 1234351-14-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 橙酮类黄酮
• 英文名称: (Z)-2-(3-chlorobenzylidene)-4,6-dihydroxybenzofuran-3(2H)-one
• 英文别名: 2-(3'-chlorobenzylidene)-4,6-dihydroxybenzofuran-3(2H)-one；(2Z)-2-[(3-chlorophenyl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one
• CAS: 1234351-14-4
• 化学式: C₁₅H₉ClO₄
• 分子量: 288.687
• InChiKey: LWVKPNYRVVIXDQ-ACAGNQJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,6-二羟基-3-苯并呋喃酮 、 3-氯苯甲醛 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 以87%的产率得到(Z)-2-(3-chlorobenzylidene)-4,6-dihydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  天然产物具有抗癌活性的PIM1抑制剂的基于结构的虚拟筛选和从头设计

  摘要：

  背景：由于细胞增殖的增强和细胞凋亡的抑制作用，莫洛尼氏鼠白血病（PIM）1激酶的前病毒插入位点已成为多种人类癌症的治疗靶标。方法：为了鉴定有效的PIM1激酶抑制剂，通过引入适当的脱水能项改善了蛋白质-配体结合自由能功能，对植物来源的天然产物进行了基于结构的虚拟筛选和从头设计。结果：作为后续酶抑制试验的结果，发现了四类PIM1激酶抑制剂，其生化潜能范围从低微摩尔水平到亚微摩尔水平。大量对接模拟的结果表明，抑制活性源于多个氢键的形成以及ATP结合位点的疏水相互作用。通过化学修饰2-亚苄基苯并呋喃3（2）来优化生化效能H）-一个支架导致发现了几种对人乳腺癌细胞系具有抗增殖活性的纳摩尔抑制剂。结论：这些新的PIM1激酶抑制剂有望成为抗癌药物开发的新起点。

  DOI：

  10.3390/ph14030275

文献信息

• Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
  作者：Chong-Yew Lee、Eng-Hui Chew、Mei-Lin Go

  DOI：10.1016/j.ejmech.2010.03.023

  日期：2010.7

  The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P) H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E-LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity. (c) 2010 Elsevier Masson SAS. All rights reserved.
• Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products
  作者：Hwangseo Park、Jinwon Jeon、Kewon Kim、Soyeon Choi、Sungwoo Hong

  DOI：10.3390/ph14030275

  日期：——

  potency by chemical modifications of the 2-benzylidenebenzofuran-3(2H)-one scaffold led to the discovery of several nanomolar inhibitors with antiproliferative activities against human breast cancer cell lines. Conclusions: these new PIM1 kinase inhibitors are anticipated to serve as a new starting point for the development of anticancer medicine.

  背景：由于细胞增殖的增强和细胞凋亡的抑制作用，莫洛尼氏鼠白血病（PIM）1激酶的前病毒插入位点已成为多种人类癌症的治疗靶标。方法：为了鉴定有效的PIM1激酶抑制剂，通过引入适当的脱水能项改善了蛋白质-配体结合自由能功能，对植物来源的天然产物进行了基于结构的虚拟筛选和从头设计。结果：作为后续酶抑制试验的结果，发现了四类PIM1激酶抑制剂，其生化潜能范围从低微摩尔水平到亚微摩尔水平。大量对接模拟的结果表明，抑制活性源于多个氢键的形成以及ATP结合位点的疏水相互作用。通过化学修饰2-亚苄基苯并呋喃3（2）来优化生化效能H）-一个支架导致发现了几种对人乳腺癌细胞系具有抗增殖活性的纳摩尔抑制剂。结论：这些新的PIM1激酶抑制剂有望成为抗癌药物开发的新起点。