capsicodendrin | 74749-35-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: capsicodendrin
• 英文别名: CPCD；[(1S,2S,7S,8R,13S)-15-[(1S,4R,4aS,8aS)-4-acetyloxy-1-formyl-1-hydroxy-5,5,8a-trimethyl-4a,6,7,8-tetrahydro-4H-naphthalen-2-yl]-11-hydroxy-2,6,6-trimethyl-12,14,16-trioxatetracyclo[8.6.0.01,13.02,7]hexadec-9-en-8-yl] acetate
• CAS: 74749-35-2
• 化学式: C₃₄H₄₈O₁₀
• 分子量: 616.749
• InChiKey: ASRYDWWUAZEWIH-QXSHUVCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  capsicodendrin 以 氘代二甲亚砜 为溶剂， 生成 (1S,4R,4aS,8aS)-4-(乙酰氧基)-1,4,4a,5,6,7,8,8a-八氢-1-羟基-5,5,8a-三甲基-1,2-萘二甲醛
  参考文献：
  名称：

  Capsicodendrin from Cinnamosma fragrans Exhibits Antiproliferative and Cytotoxic Activity in Human Leukemia Cells: Modulation by Glutathione

  摘要：

  Capsicodendrin (CPCD, 1), an epimeric mixture of a dimeric drimane-type sesquiterpene, is one of the major compounds present in the three endemic species of Madagascan traditional chemopreventive plants: Cinnamosma species (C. fragrans, C. macrocarpa, and C. madagascariensis). Despite the popular use of Cinnamosma in Madagascan traditional medicine and the reported antiproliferative properties of CPCD, elucidation of its mechanism(s) of action is still to be accomplished. In the present study, CPCD at low micromolar concentrations was cytotoxic and induced apoptosis in human myeloid leukemia cells in a time- and concentration-dependent manner. The activity of CPCD in HL-60 and K562 cells was modulated by glutathione (GSH), since depletion of this intracellular thiol-based antioxidant with buthionine sulfoximine resulted in significantly (p < 0.05) greater potency in antiproliferation assays. GSH depletion also significantly potentiated the cytotoxic activity in CPCD-treated human HL-60 cells. Single-cell gel electrophoresis (Comet) assays revealed that GSH depletion in HL-60 cells enhanced the formation of DNA strand breaks in the presence of CPCD. Although CPCD does not contain an obvious Michael acceptor in its structure, H-1 NMR analyses indicated that cinnamodial (2), a monomer of CPCD, was formed within a few hours when dissolved in DMSO- d(6) and interacts with GSH to form a covalent bond via Michael addition at the C-7 carbon. Together the results strongly suggest that 2 is responsible for the DNA-damaging, pro-apoptotic, and cytotoxic effects of CPCD and that depletion of GSH enhances overall activity by diminishing covalent interaction between GSH and this 2-alkenal decomposition product of CPCD.

  DOI：

  10.1021/acs.jnatprod.7b00887

文献信息

• Capsicodendrin from <i>Cinnamosma fragrans</i> Exhibits Antiproliferative and Cytotoxic Activity in Human Leukemia Cells: Modulation by Glutathione
  作者：Soumendrakrishna Karmahapatra、Corey Kientz、Shruthi Shetty、Jack C. Yalowich、L. Harinantenaina Rakotondraibe

  DOI：10.1021/acs.jnatprod.7b00887

  日期：2018.3.23

  Capsicodendrin (CPCD, 1), an epimeric mixture of a dimeric drimane-type sesquiterpene, is one of the major compounds present in the three endemic species of Madagascan traditional chemopreventive plants: Cinnamosma species (C. fragrans, C. macrocarpa, and C. madagascariensis). Despite the popular use of Cinnamosma in Madagascan traditional medicine and the reported antiproliferative properties of CPCD, elucidation of its mechanism(s) of action is still to be accomplished. In the present study, CPCD at low micromolar concentrations was cytotoxic and induced apoptosis in human myeloid leukemia cells in a time- and concentration-dependent manner. The activity of CPCD in HL-60 and K562 cells was modulated by glutathione (GSH), since depletion of this intracellular thiol-based antioxidant with buthionine sulfoximine resulted in significantly (p < 0.05) greater potency in antiproliferation assays. GSH depletion also significantly potentiated the cytotoxic activity in CPCD-treated human HL-60 cells. Single-cell gel electrophoresis (Comet) assays revealed that GSH depletion in HL-60 cells enhanced the formation of DNA strand breaks in the presence of CPCD. Although CPCD does not contain an obvious Michael acceptor in its structure, H-1 NMR analyses indicated that cinnamodial (2), a monomer of CPCD, was formed within a few hours when dissolved in DMSO- d(6) and interacts with GSH to form a covalent bond via Michael addition at the C-7 carbon. Together the results strongly suggest that 2 is responsible for the DNA-damaging, pro-apoptotic, and cytotoxic effects of CPCD and that depletion of GSH enhances overall activity by diminishing covalent interaction between GSH and this 2-alkenal decomposition product of CPCD.