Colchiceinamid | 3123-89-5

• 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: Colchiceinamid
• 英文别名: N-[(7S)-10-amino-1,2,3-trimethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 3123-89-5
• 化学式: C₂₁H₂₄N₂O₅
• 分子量: 384.432
• InChiKey: JWDFWIZNGSOUGC-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Colchiceinamid 在 sodium hydroxide 、 sodium carbonate 作用下， 以 乙醚 为溶剂， 反应 25.0h， 生成 原秋水仙碱
  参考文献：
  名称：

  Fluorinated colchicinoids: antitubulin and cytotoxic properties

  摘要：

  The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cell lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug-resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent.

  DOI：

  10.1021/jm00115a026
• 作为产物：
  描述：

  秋水仙碱 在 ammonium hydroxide 作用下， 生成 Colchiceinamid
  参考文献：
  名称：

  抗肿瘤药。第186部分：作为细胞毒性DNA拓扑异构酶II抑制剂的去甲基colchiceinamide类似物的合成和生物学评估。

  摘要：

  秋水仙酰胺（2）及其类似物（3-10）的去甲基化提供了一类新的哺乳动物DNA拓扑异构酶II抑制剂（2a-10a），而没有表现出微管蛋白抑制活性。在药物浓度为100 microM时，所有目标化合物均抑制拓扑异构酶II的催化活性。体外细胞毒性试验表明，化合物3a和8a对MCF-7乳腺癌细胞系（IC50分别为0.36和0.48微克/ mL）和CAKI-1肾癌细胞系（ IC50分别为0.72和0.96微克/毫升。

  DOI：

  10.1016/s0968-0896(98)00165-5

文献信息

• Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives
  作者：Adam Huczyński、Urszula Majcher、Ewa Maj、Joanna Wietrzyk、Jan Janczak、Mahshad Moshari、Jack A. Tuszynski、Franz Bartl

  DOI：10.1016/j.bioorg.2016.01.002

  日期：2016.2

  different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to

  为了产生更有效的抗癌剂，已经合成了一系列秋水仙碱的五个结构上不同的衍生物。这些化合物在光谱和结构上进行了表征，并评估了它们对四种人类肿瘤细胞系（HL-60，HL-60 / vinc，LoVo，LoVo / DX）的抗增殖活性。另外，使用涉及秋水仙碱衍生物与β-微管蛋白的分子对接的计算方法来计算所研究化合物的活性。实验和计算结果非常吻合，表明秋水仙碱衍生物的抗有丝分裂活性可以使用计算模型方法轻松预测。
• Colchicine derivatives with potent anticancer activity and reduced P-glycoprotein induction liability
  作者：Baljinder Singh、Ashok Kumar、Prashant Joshi、Santosh K. Guru、Suresh Kumar、Zahoor A. Wani、Girish Mahajan、Aashiq Hussain、Asif Khurshid Qazi、Ajay Kumar、Sonali S. Bharate、Bishan D. Gupta、Parduman R. Sharma、Abid Hamid、Ajit K. Saxena、Dilip M. Mondhe、Shashi Bhushan、Sandip B. Bharate、Ram A. Vishwakarma

  DOI：10.1039/c5ob00406c

  日期：——

  Colchicine derivatives with reduced P-gp induction liability have been identified.

  已经确定了几种减少P-糖蛋白诱导责任的秋水仙碱衍生物。
• Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1‐Activated Prodrugs as Antiviral Agents
  作者：Michael Richter、Veaceslav Boldescu、Dominik Graf、Felix Streicher、Anatoli Dimoglo、Ralf Bartenschlager、Christian D. Klein

  DOI：10.1002/cmdc.201800641

  日期：2019.2.19

  these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed

  最近的研究表明，微管蛋白可能是登革热（DENV）和寨卡病毒（ZIKV）等载体传播的黄病毒的宿主因子，并且已证明微管蛋白聚合抑制剂（例如秋水仙碱）会减少病毒复制。但是，毒性限制了这些化合物的应用。在本文中，我们报道了基于康普他汀和秋水仙碱衍生物的前药，其包含人羧酸酯酶的酯裂解位点，人羧酸酯酶是DENV靶向的单核细胞和肝细胞中高度丰富的酶。相对于其母体化合物，这些前药的细胞毒性降低了几个数量级。所有含有亮氨酸酯的合成前药在体外都被酯酶水解。与以前的报道相反，苯甘氨酸酯未被人的羧酸酯酶切割。在低微摩尔和亚微摩尔浓度下，观察到了康布雷他汀，秋水仙碱和某些前药对细胞培养物中DENV和ZIKV的抗病毒活性。另外，进行对接研究以了解所研究化合物与微管蛋白的结合模式。
• Methods of treating cancer using compounds containing a vascular disrupting agent
  申请人：Ellipses Pharma Limited

  公开号：US10912839B2

  公开（公告）日：2021-02-09

  The present invention relates to prodrugs of vascular disrupting agents comprising a vascular disrupting agent (VDA) associated with a MMP proteolytic cleavage site and to the use of such prodrugs in the targeted treatment of cancer.

  本发明涉及血管破坏剂的原药，包括与 MMP 蛋白水解裂解位点相关的血管破坏剂 (VDA)，以及此类原药在癌症靶向治疗中的应用。
• Colchicine. Derivatives of Trimethylcolchicinic Acid^1,2
  作者：Robert F. Raffauf、Ann L. Farren、Glenn E. Ullyot

  DOI：10.1021/ja01117a044

  日期：1953.11