(S,S)-1,4-bis{2-[3-tert-butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionylamino]ethylamino}-9,10-anthracenedione | 1015236-75-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: (S,S)-1,4-bis{2-[3-tert-butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionylamino]ethylamino}-9,10-anthracenedione
• 英文别名: 9H-fluoren-9-ylmethyl N-[(2S)-1-[2-[[4-[2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]ethylamino]-9,10-dioxoanthracen-1-yl]amino]ethylamino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]carbamate
• CAS: 1015236-75-5
• 化学式: C₆₂H₆₆N₆O₁₀
• 分子量: 1055.24
• InChiKey: JZGRNAPMALRBIX-XWQGWOARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  78
• 可旋转键数：
  24
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  212
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S,S)-1,4-bis{2-[3-tert-butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionylamino]ethylamino}-9,10-anthracenedione 在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以73%的产率得到(2S)-2-amino-N-[2-[[4-[2-[[(2S)-2-amino-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]ethylamino]-9,10-dioxoanthracen-1-yl]amino]ethyl]-3-[(2-methylpropan-2-yl)oxy]propanamide
  参考文献：
  名称：

  Synthesis, DNA binding, and cytotoxicity of 1,4-bis(2-amino-ethylamino)anthraquinone–amino acid conjugates

  摘要：

  Two series of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates (BACs), ametantrone (AT)-amino acid conjugates (AACs) and mitoxantrone (MX)-amino acid conjugates (MACs), were designed and synthesized. The DNA binding of BACs was evaluated by DNA thermal denaturation experiment. In the series, the methionine-substituted BACs had the weakest DNA binding, while the lysine-substituted BACs had the highest T-m values. The abilities of BACs to inhibit the growth of MCF-7, NCI-H460, SF-268, and PC-3 cell lines were determined. L-Met-MAC 16 and L-Lys-MAC 20 were the most potent growth inhibitors. MAC 16 was more cytotoxic than MX, whereas the T-m of MAC 16 was much lower than that of MX In contrast to MAC 16, L-Lys-MAC 20 demonstrated higher T-m than MX. These data suggested that Met-BACs possessed a different pharmacological profile, in which the ability to stabilize DNA is not parallel to the ability to kill cancer cells, from that of AT and MX. The primary mechanism of cytotoxicity for MAC 16 was most likely through TOP2 poisoning. Therefore, MAC 16 may provide a lead for the development of novel generations of anthraquinone-type antitumor agents. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.012
• 作为产物：
  描述：

  1,4-di-(2-aminoethylamino)anthraquinone 、 FMOC-O-叔丁基-L-丝氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以54%的产率得到(S,S)-1,4-bis{2-[3-tert-butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionylamino]ethylamino}-9,10-anthracenedione
  参考文献：
  名称：

  Synthesis, DNA binding, and cytotoxicity of 1,4-bis(2-amino-ethylamino)anthraquinone–amino acid conjugates

  摘要：

  Two series of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates (BACs), ametantrone (AT)-amino acid conjugates (AACs) and mitoxantrone (MX)-amino acid conjugates (MACs), were designed and synthesized. The DNA binding of BACs was evaluated by DNA thermal denaturation experiment. In the series, the methionine-substituted BACs had the weakest DNA binding, while the lysine-substituted BACs had the highest T-m values. The abilities of BACs to inhibit the growth of MCF-7, NCI-H460, SF-268, and PC-3 cell lines were determined. L-Met-MAC 16 and L-Lys-MAC 20 were the most potent growth inhibitors. MAC 16 was more cytotoxic than MX, whereas the T-m of MAC 16 was much lower than that of MX In contrast to MAC 16, L-Lys-MAC 20 demonstrated higher T-m than MX. These data suggested that Met-BACs possessed a different pharmacological profile, in which the ability to stabilize DNA is not parallel to the ability to kill cancer cells, from that of AT and MX. The primary mechanism of cytotoxicity for MAC 16 was most likely through TOP2 poisoning. Therefore, MAC 16 may provide a lead for the development of novel generations of anthraquinone-type antitumor agents. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.012

文献信息

• Synthesis, DNA binding, and cytotoxicity of 1,4-bis(2-amino-ethylamino)anthraquinone–amino acid conjugates
  作者：Ling-Wei Hsin、Hui-Po Wang、Pi-Hung Kao、On Lee、Wan-Ru Chen、Hung-Wei Chen、Jih-Hwa Guh、Ya-Ling Chan、Chin-Ping His、Ming-Show Yang、Tsai-Kun Li、Chieh-Hua Lee

  DOI：10.1016/j.bmc.2007.10.012

  日期：2008.1

  Two series of 1,4-bis(2-amino-ethylamino)anthraquinone-amino acid conjugates (BACs), ametantrone (AT)-amino acid conjugates (AACs) and mitoxantrone (MX)-amino acid conjugates (MACs), were designed and synthesized. The DNA binding of BACs was evaluated by DNA thermal denaturation experiment. In the series, the methionine-substituted BACs had the weakest DNA binding, while the lysine-substituted BACs had the highest T-m values. The abilities of BACs to inhibit the growth of MCF-7, NCI-H460, SF-268, and PC-3 cell lines were determined. L-Met-MAC 16 and L-Lys-MAC 20 were the most potent growth inhibitors. MAC 16 was more cytotoxic than MX, whereas the T-m of MAC 16 was much lower than that of MX In contrast to MAC 16, L-Lys-MAC 20 demonstrated higher T-m than MX. These data suggested that Met-BACs possessed a different pharmacological profile, in which the ability to stabilize DNA is not parallel to the ability to kill cancer cells, from that of AT and MX. The primary mechanism of cytotoxicity for MAC 16 was most likely through TOP2 poisoning. Therefore, MAC 16 may provide a lead for the development of novel generations of anthraquinone-type antitumor agents. (C) 2007 Elsevier Ltd. All rights reserved.