5-(2-(2-((7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)oxy)ethoxy)ethoxy)-5-oxopentanoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 5-(2-(2-((7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)oxy)ethoxy)ethoxy)-5-oxopentanoic acid
• 英文别名: 5-[2-[2-[7-(Diethylamino)-2-oxochromene-3-carbonyl]oxyethoxy]ethoxy]-5-oxopentanoic acid；5-[2-[2-[7-(diethylamino)-2-oxochromene-3-carbonyl]oxyethoxy]ethoxy]-5-oxopentanoic acid
• 化学式: C₂₃H₂₉NO₉
• 分子量: 463.485
• InChiKey: YZYYHMMOHHJBGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  冬凌草甲素 、 5-(2-(2-((7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)oxy)ethoxy)ethoxy)-5-oxopentanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到
  参考文献：
  名称：

  Probing the Anticancer Action of Oridonin with Fluorescent Analogues: Visualizing Subcellular Localization to Mitochondria

  摘要：

  Oridonin (1) is a complex ent-kaurane diterpenoid exhibiting remarkable antitumor activity. However, the detailed mechanism or cellular target that underlies this activity has not yet been identified. Herein, we report an efficient approach for exploring the anticancer mechanism of oridonin through development of the potent fluorescent analogues. A series of novel fluorescent oridonin probes linked with coumarin moieties were designed, synthesized, and characterized. Fluorescence microscopy and confocal imaging studies suggested that fluorescent oridonin probe 17d was rapidly taken up into tumor cells and the mitochondrion was the main site of its accumulation. Moreover, we confirmed that cytochrome c played an important role in oridonin induced mitochondrion-mediated apoptosis and alpha,beta-unsaturated ketone is the active moiety of oridonin, which is crucial to its uptake, localization, and cytotoxicity. Our results provide new insights on the molecular mechanism of oridonin and would be useful for its further development into an antitumor agent.

  DOI：

  10.1021/acs.jmedchem.6b00408
• 作为产物：
  描述：

  7-(二乙胺基)香豆素-3-甲酸乙酯 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 48.0h， 生成 5-(2-(2-((7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)oxy)ethoxy)ethoxy)-5-oxopentanoic acid
  参考文献：
  名称：

  Probing the Anticancer Action of Oridonin with Fluorescent Analogues: Visualizing Subcellular Localization to Mitochondria

  摘要：

  Oridonin (1) is a complex ent-kaurane diterpenoid exhibiting remarkable antitumor activity. However, the detailed mechanism or cellular target that underlies this activity has not yet been identified. Herein, we report an efficient approach for exploring the anticancer mechanism of oridonin through development of the potent fluorescent analogues. A series of novel fluorescent oridonin probes linked with coumarin moieties were designed, synthesized, and characterized. Fluorescence microscopy and confocal imaging studies suggested that fluorescent oridonin probe 17d was rapidly taken up into tumor cells and the mitochondrion was the main site of its accumulation. Moreover, we confirmed that cytochrome c played an important role in oridonin induced mitochondrion-mediated apoptosis and alpha,beta-unsaturated ketone is the active moiety of oridonin, which is crucial to its uptake, localization, and cytotoxicity. Our results provide new insights on the molecular mechanism of oridonin and would be useful for its further development into an antitumor agent.

  DOI：

  10.1021/acs.jmedchem.6b00408

文献信息

• Probing the Anticancer Action of Oridonin with Fluorescent Analogues: Visualizing Subcellular Localization to Mitochondria
  作者：Shengtao Xu、Shanshan Luo、Hong Yao、Hao Cai、Xiaoming Miao、Fang Wu、Dong-Hua Yang、Xiaoming Wu、Weijia Xie、Hequan Yao、Zhe-Sheng Chen、Jinyi Xu

  DOI：10.1021/acs.jmedchem.6b00408

  日期：2016.5.26

  Oridonin (1) is a complex ent-kaurane diterpenoid exhibiting remarkable antitumor activity. However, the detailed mechanism or cellular target that underlies this activity has not yet been identified. Herein, we report an efficient approach for exploring the anticancer mechanism of oridonin through development of the potent fluorescent analogues. A series of novel fluorescent oridonin probes linked with coumarin moieties were designed, synthesized, and characterized. Fluorescence microscopy and confocal imaging studies suggested that fluorescent oridonin probe 17d was rapidly taken up into tumor cells and the mitochondrion was the main site of its accumulation. Moreover, we confirmed that cytochrome c played an important role in oridonin induced mitochondrion-mediated apoptosis and alpha,beta-unsaturated ketone is the active moiety of oridonin, which is crucial to its uptake, localization, and cytotoxicity. Our results provide new insights on the molecular mechanism of oridonin and would be useful for its further development into an antitumor agent.