Doxo-SE | 636608-27-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: Doxo-SE
• 英文别名: Doxo-14-succinic ester；Doxo-14-SE；14-Doxorubicinyl Succinate Ester；4-[2-[(2S,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-oxoethoxy]-4-oxobutanoic acid
• CAS: 636608-27-0
• 化学式: C₃₁H₃₃NO₁₄
• 分子量: 643.601
• InChiKey: JPXVYJIZQVOUMV-COAHAIOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  249
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  阿霉素 在 哌啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 Doxo-SE
  参考文献：
  名称：

  Synthesis, Anticancer Activities, and Cellular Uptake Studies of Lipophilic Derivatives of Doxorubicin Succinate

  摘要：

  A number of lipophilic 14-substituted derivatives of doxorubicin were synthesized through conjugation of doxorubicin-14-hemisuccinate with different fatty amines or tetradecanol to enhance the lipophilicity, cellular uptake, and cellular retention for sustained anticancer activity. The conjugates inhibited the cell proliferation of human leukemia (CCRF-CEM, 69-76%), colon adenocarcinoma (HT-29, 60-77%), and breast adenocarcinoma (MDA-MB-361, 66-71%) cells at a concentration of 1 mu M after 96-120 h of incubation. The N-tetradecylamido derivative of doxorubicin 14-succinate (10) exhibited consistently comparable antiproliferative activity to doxorubicin in a time-dependent manner (IC50 = 77 nM in CCRF-CEM cells). Flow cytometry analysis showed a 3-fold more cellular uptake of 10 than doxorubicin in SK-OV-3 cells. Confocal microscopy revealed that the conjugate was distributed in cytoplasmic and perinuclear areas during the first 1 h of incubation and slowly relocalized in the nucleus after 24 h. The cellular hydrolysis study showed that 98% of compound 10 was hydrolyzed intracellularly within 48 h and released doxorubicin.

  DOI：

  10.1021/jm201653u

文献信息

• Tong, Rong; Cheng, Jianjun, Journal of the American Chemical Society, 2009, vol. 131, p. 4744 - 4754
  作者：Tong, Rong、Cheng, Jianjun

  DOI：——

  日期：——
• Synthesis, Anticancer Activities, and Cellular Uptake Studies of Lipophilic Derivatives of Doxorubicin Succinate
  作者：Bhupender S. Chhikara、Deendayal Mandal、Keykavous Parang

  DOI：10.1021/jm201653u

  日期：2012.2.23

  A number of lipophilic 14-substituted derivatives of doxorubicin were synthesized through conjugation of doxorubicin-14-hemisuccinate with different fatty amines or tetradecanol to enhance the lipophilicity, cellular uptake, and cellular retention for sustained anticancer activity. The conjugates inhibited the cell proliferation of human leukemia (CCRF-CEM, 69-76%), colon adenocarcinoma (HT-29, 60-77%), and breast adenocarcinoma (MDA-MB-361, 66-71%) cells at a concentration of 1 mu M after 96-120 h of incubation. The N-tetradecylamido derivative of doxorubicin 14-succinate (10) exhibited consistently comparable antiproliferative activity to doxorubicin in a time-dependent manner (IC50 = 77 nM in CCRF-CEM cells). Flow cytometry analysis showed a 3-fold more cellular uptake of 10 than doxorubicin in SK-OV-3 cells. Confocal microscopy revealed that the conjugate was distributed in cytoplasmic and perinuclear areas during the first 1 h of incubation and slowly relocalized in the nucleus after 24 h. The cellular hydrolysis study showed that 98% of compound 10 was hydrolyzed intracellularly within 48 h and released doxorubicin.