(2,5-dioxopyrrolidin-1-yl) 5-oxo-5-[[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]amino]pentanoate | 725735-06-8

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: (2,5-dioxopyrrolidin-1-yl) 5-oxo-5-[[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]amino]pentanoate
• CAS: 725735-06-8
• 化学式: C₂₉H₃₂N₂O₁₀
• 分子量: 568.58
• InChiKey: NOQKXPMMIQZERA-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2,5-dioxopyrrolidin-1-yl) 5-oxo-5-[[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]amino]pentanoate 、 以 二甲基亚砜 为溶剂， 反应 1.0h， 以34%的产率得到
  参考文献：
  名称：

  Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin

  摘要：

  Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B-12) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC50 values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.

  DOI：

  10.1021/jo049953w
• 作为产物：
  描述：

  秋水仙碱 在 N-甲基吗啉 、 甲醇 、 4-二甲氨基吡啶 、 sodium methylate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 27.83h， 生成 (2,5-dioxopyrrolidin-1-yl) 5-oxo-5-[[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]amino]pentanoate
  参考文献：
  名称：

  Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin

  摘要：

  Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B-12) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC50 values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.

  DOI：

  10.1021/jo049953w

文献信息

• Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin
  作者：Joshua D. Bagnato、Alanna L. Eilers、Robert A. Horton、Charles B. Grissom

  DOI：10.1021/jo049953w

  日期：2004.12.1

  Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B-12) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC50 values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.