cochinchinoxanthone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: cochinchinoxanthone
• 英文别名: 6,8-Dihydroxy-17,17-dimethyl-15-(3-methylbut-2-enyl)-3,16-dioxapentacyclo[11.4.1.02,11.02,15.04,9]octadeca-4,6,8,11-tetraene-10,14-dione；6,8-dihydroxy-17,17-dimethyl-15-(3-methylbut-2-enyl)-3,16-dioxapentacyclo[11.4.1.02,11.02,15.04,9]octadeca-4,6,8,11-tetraene-10,14-dione
• 化学式: C₂₃H₂₄O₆
• 分子量: 396.44
• InChiKey: XCRBRZWMQVMPIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  cochinchinoxanthone 、 对甲苯磺酸三缩乙二醇单甲醚酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以75%的产率得到CR170A
  参考文献：
  名称：

  Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer

  摘要：

  Inflammatory breast cancer (IBC) is a highly metastatic, lethal form of breast cancer that lacks targeted therapeutic strategies. Inspired by the promising cytotoxicity of gambogic acid and related caged xanthones in spheroids(MARY-X), an in vitro preclinical IBC model, we constructed a library of synthetic analogs and performed structure-activity relationship studies. The studies revealed that functionalizing the A-ring of the caged xanthone framework can significantly affect potency. Specifically, introduction of hydroxyl or fluorine groups at discrete positions of the A-ring leads to enhanced cytotoxicity at sub-micromolar concentrations. These compounds induce complete dissolution of spheroids(MARY-X) with subsequent apoptosis of both the peripherally- and centrally-located cells, proliferative and quiescent-prone (e.g. hypoxic), respectively. These results highlight the structural flexibility and pharmacological potential of the caged xanthone motif for the design of IBC-targeting therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.047
• 作为产物：
  描述：

  7-hydroxy-9-(methoxymethoxy)-2,2-diphenyl-6H-[1,3]dioxolo[4,5-c]xanthen-6-one 在 盐酸 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 48.0h， 生成 cochinchinoxanthone
  参考文献：
  名称：

  Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer

  摘要：

  Inflammatory breast cancer (IBC) is a highly metastatic, lethal form of breast cancer that lacks targeted therapeutic strategies. Inspired by the promising cytotoxicity of gambogic acid and related caged xanthones in spheroids(MARY-X), an in vitro preclinical IBC model, we constructed a library of synthetic analogs and performed structure-activity relationship studies. The studies revealed that functionalizing the A-ring of the caged xanthone framework can significantly affect potency. Specifically, introduction of hydroxyl or fluorine groups at discrete positions of the A-ring leads to enhanced cytotoxicity at sub-micromolar concentrations. These compounds induce complete dissolution of spheroids(MARY-X) with subsequent apoptosis of both the peripherally- and centrally-located cells, proliferative and quiescent-prone (e.g. hypoxic), respectively. These results highlight the structural flexibility and pharmacological potential of the caged xanthone motif for the design of IBC-targeting therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.047

文献信息

• Garcinia Xanthones as Orally Active Antitumor Agents
  作者：Xiaojin Zhang、Xiang Li、Haopeng Sun、Xiaojian Wang、Li Zhao、Yuan Gao、Xiaorong Liu、Shenglie Zhang、Yanyan Wang、Yingrui Yang、Su Zeng、Qinglong Guo、Qidong You

  DOI：10.1021/jm301593r

  日期：2013.1.10

  Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D-7.4, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.