O,O'-diethyl{[(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)formamido](2-methoxyphenyl)methyl}phosphonate | 1537944-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: O,O'-diethyl{[(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)formamido](2-methoxyphenyl)methyl}phosphonate
• 英文别名: O,O'-diethyl {[2-(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)acetylamino](2-methoxyphenyl)methyl}phosphonate；N-[diethoxyphosphoryl-(2-methoxyphenyl)methyl]-4,5-dihydroxy-9,10-dioxoanthracene-2-carboxamide
• CAS: 1537944-47-0
• 化学式: C₂₇H₂₆NO₉P
• 分子量: 539.478
• InChiKey: HACPXPTUYWMAJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  148.46
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  diethyl (((2-methoxybenzylidene)amino)(2-methoxyphenyl)methyl)phosphonate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 反应 7.75h， 生成 O,O'-diethyl{[(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)formamido](2-methoxyphenyl)methyl}phosphonate
  参考文献：
  名称：

  Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates

  摘要：

  Several rhein alpha-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 mu M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.030

文献信息

• 大黄酸氨基膦酸酯衍生物及其合成方法和应用
  申请人：广西师范大学

  公开号：CN103524555B

  公开（公告）日：2016-01-20

  本发明公开了一系列大黄酸氨基膦酸酯衍生物及它们的合成方法和应用。所述大黄酸氨基膦酸酯衍生物的合成方法为：以大黄酸和α-氨基膦酸酯为原料，溶于极性溶剂中，在催化剂HOBT和缩合剂EDAC存在的条件下反应至完全；向反应液中加入三氯甲烷，水洗，收集有机层，上硅胶柱层析，用由体积比为1:4～100的乙酸乙酯和石油醚组成的混合溶剂洗脱，即得到相应的衍生物。所述的大黄酸氨基膦酸酯衍生物，其结构通式如下式(I)所示：其中，R为对溴苯、邻溴苯、间溴苯、对氟苯、邻氟苯、对氯苯、间氯苯、邻氯苯、间甲氧基苯、邻甲氧基苯、苯、萘、对甲氧基苯、间甲基苯、对甲基苯、间氟苯或蒽。
• Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates
  作者：Gui-yang Yao、Man-yi Ye、Ri-zhen Huang、Ya-jun Li、Ying-ming Pan、Qing Xu、Zhi-Xin Liao、Heng-shan Wang

  DOI：10.1016/j.bmcl.2013.12.030

  日期：2014.1

  Several rhein alpha-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 mu M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA. (C) 2013 Elsevier Ltd. All rights reserved.