3′,5-diallyl-4′-(pentyloxy)-[1,1′-biphenyl]-2-ol | 1315334-01-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3′,5-diallyl-4′-(pentyloxy)-[1,1′-biphenyl]-2-ol
• 英文别名: Magreth-18b；2-(4-pentoxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol
• CAS: 1315334-01-0
• 化学式: C₂₃H₂₈O₂
• 分子量: 336.474
• InChiKey: WIQKQADUKUIMKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-碘戊烷 、 和厚朴酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以43%的产率得到3′,5-diallyl-4′-(pentyloxy)-[1,1′-biphenyl]-2-ol
  参考文献：
  名称：

  Anticancer Effects of Honokiol via Mitochondrial Dysfunction Are Strongly Enhanced by the Mitochondria-Targeting Carrier Berberine

  摘要：

  Mitochondrion is a favorable therapeutic target in cancer, given its regulation of bioenergetics and cell death. Honokiol exhibits antiproliferative effects through mitochondria-mediated death signaling. To enhance its anticancer potential and selectivity, we conjugated honokiol to berberine, a mitochondria-targeting carrier. All designed derivatives displayed 1 order of magnitude increased cytotoxicity compared with the parent compounds, especially with massive cytoplasmic vacuoles. Biological evaluation demonstrated the representative compound 6b localized within the mitochondria, and mitochondrial dilation resulted in vacuolization. 6b induced vacuolation-associated cell death and apoptosis with obvious mitochondrial dysfunction, as demonstrated by booming reactive oxygen species generation, opening mitochondrial permeability transition pore, and reducing mitochondrial membrane potential. The targeting property also conferred 6b with selectivity for tumor cells compared to normal cells. 6b inhibited cancer cell proliferation in the zebrafish xenograft model. These results demonstrate that berberine-linked honokiol derivatives open up a direction for novel mitochondrial-targeting antitumor agents.

  DOI：

  10.1021/acs.jmedchem.0c00881

文献信息

• Mechanisms of Osteoclastogenesis Inhibition by a Novel Class of Biphenyl-Type Cannabinoid CB2 Receptor Inverse Agonists
  作者：Wolfgang Schuehly、Juan Manuel Viveros Paredes、Jonas Kleyer、Antje Huefner、Sharon Anavi-Goffer、Stefan Raduner、Karl-Heinz Altmann、Jürg Gertsch

  DOI：10.1016/j.chembiol.2011.05.012

  日期：2011.8

  The cannabinoid CB2 receptor is known to modulate osteoclast function by poorly understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O-methylhonokiol (MH) is a CB2 receptor-selective antiosteoclastogenic lead structure (K-i < 50 nM). Intriguingly, MH triggers a simultaneous G(i) inverse agonist response and a strong CB2 receptor-dependent increase in intracellular calcium. The most active inverse agonists from a library of MH derivatives inhibited osteoclastogenesis in RANK ligand-stimulated RAW264.7 cells and primary human macrophages. Moreover, these ligands potently inhibited the osteoclastogenic action of endocannabinoids. Our data show that CB2 receptor-mediated cAMP formation, but not intracellular calcium, is crucially involved in the regulation of osteoclastogenesis, primarily by inhibiting macrophage chemotaxis and TNF-alpha expression. MH is an easily accessible CB2 receptor-selective scaffold that exhibits a novel type of functional heterogeneity.
• MITO-HONOKIOL COMPOUNDS AND METHODS OF SYNTHESIS AND USE THEREOF
  申请人：THE MEDICAL COLLEGE OF WISCONSIN, INC.

  公开号：US20180134737A1

  公开（公告）日：2018-05-17

  The present invention provides mito-honokiol compounds, pharmaceutical compositions thereof, and methods of using the mito-honokiol compounds in the treatment of cancer.
• Anticancer Effects of Honokiol via Mitochondrial Dysfunction Are Strongly Enhanced by the Mitochondria-Targeting Carrier Berberine
  作者：Xiaojia Shi、Tao Zhang、Hongxiang Lou、Huina Song、Changhao Li、Peihong Fan

  DOI：10.1021/acs.jmedchem.0c00881

  日期：2020.10.22

  Mitochondrion is a favorable therapeutic target in cancer, given its regulation of bioenergetics and cell death. Honokiol exhibits antiproliferative effects through mitochondria-mediated death signaling. To enhance its anticancer potential and selectivity, we conjugated honokiol to berberine, a mitochondria-targeting carrier. All designed derivatives displayed 1 order of magnitude increased cytotoxicity compared with the parent compounds, especially with massive cytoplasmic vacuoles. Biological evaluation demonstrated the representative compound 6b localized within the mitochondria, and mitochondrial dilation resulted in vacuolization. 6b induced vacuolation-associated cell death and apoptosis with obvious mitochondrial dysfunction, as demonstrated by booming reactive oxygen species generation, opening mitochondrial permeability transition pore, and reducing mitochondrial membrane potential. The targeting property also conferred 6b with selectivity for tumor cells compared to normal cells. 6b inhibited cancer cell proliferation in the zebrafish xenograft model. These results demonstrate that berberine-linked honokiol derivatives open up a direction for novel mitochondrial-targeting antitumor agents.