4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-desoxypodophyllotoxin | 675199-77-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-desoxypodophyllotoxin
• 英文别名: 4β-(4-hydroxymethyl-1,2,3-triazolyl)epipodophyllotoxin；(5S,5aS,8aR,9R)-5-[4-(hydroxymethyl)triazol-1-yl]-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
• CAS: 675199-77-6
• 化学式: C₂₅H₂₅N₃O₈
• 分子量: 495.489
• InChiKey: VYEHKJZEGTZXEK-AZIXLERZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-desoxypodophyllotoxin 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-desoxypodophyllotoxin cyclopentyl carbamate
  参考文献：
  名称：

  Synthesis and cytotoxic activity on human cancer cells of carbamate derivatives of 4β-(1,2,3-triazol-1-yl)podophyllotoxin

  摘要：

  Carbamate derivatives of 4 beta-(1,2,3-triazol-1-yl)podophyllotoxin were synthesized by means of click chemistry, and their cytotoxicities against human cancer cell lines HL-60, A-549, HeLa, and HCT-8 were evaluated. Some compounds were more potent than the anticancer drug etoposide. 4'-O-Demethyl-4 beta-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-deoxypodophyllotoxin cyclopentyl carbamate, the most potent compound, induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells. Furthermore, this compound inhibited the formation of microtubules in A-549 cells and caused the inhibition of DNA topoisomerase-II. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.068
• 作为产物：
  描述：

  鬼臼毒素 在 sodium azide 、 甲烷磺酸 、 三氟乙酸 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 266.75h， 生成 4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

  摘要：

  The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of a focused library of etoposide analogues, with the identification of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings pave the way toward studying isoform-specific cellular processes by means of small molecule intervention.

  DOI：

  10.1021/acs.jmedchem.5b00473

文献信息

• 4β-[(4-Alkyl)-1,2,3-triazol-1-yl] podophyllotoxins as anticancer compounds: Design, synthesis and biological evaluation
  作者：Doma Mahendhar Reddy、Jada Srinivas、Gousia Chashoo、Ajit K. Saxena、H.M. Sampath Kumar

  DOI：10.1016/j.ejmech.2011.02.016

  日期：2011.6

  A series of 4β-[(4-alkyl)-1,2,3-triazol-1-yl] podophyllotoxin derivatives were designed in silico, synthesised by employing click chemistry approach, and evaluated for cytotoxicity against a panel of human cancer cell lines (SF-295, A-549, PC-3, Hep-2, HCT-15 and MCF-7). Majority of the compounds proved to be more potent than etoposide and select compounds exhibited significant anticancer activity

  在计算机上设计了一系列4β-[（（4-烷基）-1,2,3-三唑-1-基]鬼臼毒素衍生物，通过点击化学方法合成，并评估了其对一组人类癌细胞系的细胞毒性（SF-295，A-549，PC-3，Hep-2，HCT-15和MCF-7）。多数化合物被证明比依托泊苷更有效，某些化合物表现出显着的抗癌活性，IC 50值在0.001–1μM的范围内。DNA片段化和流式细胞仪结果表明，4β-[（（4-烷基）-1,2,3-三唑-1-基]鬼臼毒素衍生物诱导剂量依赖性细胞凋亡。对接实验表明，它们与拓扑异构酶-II的相互作用能与观察到的IC 50之间具有良好的相关性 所有这些化合物的值。