10,13-dimethyl-1,3,4,6-tetrahydroxy-helianthrone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苝醌类
• 英文名称: 10,13-dimethyl-1,3,4,6-tetrahydroxy-helianthrone
• 英文别名: 11,13,16,18-tetrahydroxy-5,24-dimethylheptacyclo[13.11.1.12,10.03,8.019,27.021,26.014,28]octacosa-1,3(8),4,6,10,12,14(28),15(27),16,18,21(26),22,24-tridecaene-9,20-dione
• 化学式: C₃₀H₁₈O₆
• 分子量: 474.469
• InChiKey: GMSRZQBWXMTFOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  36
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  115
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10,13-dimethyl-1,3,4,6-tetrahydroxy-helianthrone 在 溴 、 溶剂黄146 作用下， 反应 2.5h， 以38%的产率得到2,5-dibromo-methyl helianthrone
  参考文献：
  名称：

  Novel Methyl Helianthrones as Photosensitizers: Synthesis and Biological Evaluation¶

  摘要：

  A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alpha T3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyll helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.

  DOI：

  10.1562/2004-07-14-ra-234.1

文献信息

• POLYCYCLIC DIANTHRAQUINONES AS INHIBITORS OF INFLAMMATORY CYTOKINES
  申请人：Hazan Zadik

  公开号：US20100048728A1

  公开（公告）日：2010-02-25

  The present invention relates to the therapeutic use of polycyclic dianthraquinones including hypericin, helianthrones and helianthrone derivatives as inhibitors of the proinflammatory cytokine cascade mediated inflammatory conditions such as inflammatory bowel disease and cachexia. In addition the compositions can be used for prevention of development of inflammation, fibrosis and vasculopathy as a sequelae induced by irradiation treatment, and to the use thereof, as protective modes for the consequences of irradiation treatment in diseases such as cancers. The present invention can also be used to prevent or improve the inflammatory consequences of infections with viruses or bacteria and to prevent or treat neuroinflammatory disorders.
• [EN] POLYCYCLIC DIANTHRAQUINONES AS INHIBITORS OF INFLAMMATORY CYTOKINES<br/>[FR] DIANTHRAQUINONES POLYCYCLIQUES COMME INHIBITEURS DE CYTOKINES INFLAMMATOIRES
  申请人：HY BIOPHARMA INC

  公开号：WO2008015680A2

  公开（公告）日：2008-02-07

  [EN] The present invention relates to the therapeutic use of polycyclic dianthraquinones including hypericin, helianthrones and helianthrone derivatives as inhibitors of the proinflammatory cytokine cascade mediated inflammatory conditions such as inflammatory bowel disease and cachexia. In addition the compositions can be used for prevention of development of inflammation, fibrosis and vasculopathy as a sequelae induced by irradiation treatment, and to the use thereof, as protective modes for the consequences of irradiation treatment in diseases such as cancers. The present invention can also be used to prevent or improve the inflammatory consequences of infections with viruses or bacteria and to prevent or treat neuroinflammatory disorders.
  [FR] La présente invention concerne l'utilisation thérapeutique de dianthraquinones polycycliques comprenant l'hypericine, les hélianthrones et les dérivés d'hélianthrones comme inhibiteurs des conditions inflammatoires à médiation par la cascade de cytokines proinflammatoires, telles que la maladie intestinale inflammatoire et la cachexie. De plus, les compositions peuvent être utilisées pour la prévention du développement d'une inflammation, d'une fibrose et d'une vasculopathie constituant les séquelles d'un traitement par irradiation, et comme prévention des conséquences néfastes d'un traitement par irradiation dans les maladies telles que les cancers. La présente invention peut également être utilisée pour prévenir ou pour diminuer les conséquences inflammatoires d'infections par virus ou bactéries et pour prévenir ou traiter des troubles neuroinflammatoires.
• Novel Methyl Helianthrones as Photosensitizers: Synthesis and Biological Evaluation¶
  作者：Shai Rahimipour、Naomi Litichever-Coslovsky、Moran Alaluf、Dalia Freeman、Benjamin Ehrenberg、Lev Weiner、Yehuda Mazur、Mati Fridkin、Yitzhak Koch

  DOI：10.1562/2004-07-14-ra-234.1

  日期：——

  A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alpha T3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyll helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.