4β-N-[{furan-2-yl}methyl]amido-4'-demethyl-4-desoxypodophyllotoxin | 150060-22-3

• 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-N-[{furan-2-yl}methyl]amido-4'-demethyl-4-desoxypodophyllotoxin
• 英文别名: 4β-N-[(furan-2-yl)methyl]amino-4′-O-demethyl-4-desoxypodophyllotoxin；(5S,5aS,8aR,9R)-5-(furan-2-ylmethylamino)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
• CAS: 150060-22-3
• 化学式: C₂₆H₂₅NO₈
• 分子量: 479.486
• InChiKey: XIKUKJMJYCWEMF-QQJYNPJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (5R,5aR,8aS,9S)-9-amino-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 4β-N-[{furan-2-yl}methyl]amido-4'-demethyl-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Novel 4′-O-Demethylpodophyllotoxin Derivatives as Potential Anticancer Agents

  摘要：

  通过醛类与4′-O-去甲基鬼臼毒素反应，设计了10种4′-O-去甲基鬼臼毒素的4β-N-取代衍生物。使用MTT法评估了它们对癌细胞系（HeLa）的细胞毒性。化合物7a-7d、7f、7g和7h表现出比阳性对照依托泊苷（VP-16）更强的活性。4′-O-去甲基鬼臼毒素的4β-N-取代衍生物具有潜在的抗肿瘤活性，值得进一步研究。

  DOI：

  10.1007/s10600-022-03757-z

文献信息

• Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents
  作者：Wei-Hua Cheng、Bo Cao、Hai Shang、Cong Niu、Li-Ming Zhang、Zhong-Heng Zhang、Dan-Li Tian、Shi Zhang、Hong Chen、Zhong-Mei Zou

  DOI：10.1016/j.ejmech.2014.08.006

  日期：2014.10

  Cancer multidrug resistance (MDR) is a common cause of treatment failure in cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human cancer cell lines, HeLa, 1(562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and Cytotoxicity of Novel 4′-O-Demethylpodophyllotoxin Derivatives as Potential Anticancer Agents
  作者：Dan-li Tian、Hong Chen、Gang Luo、Chun-po Liang

  DOI：10.1007/s10600-022-03757-z

  日期：2022.7

  Ten 4β-N-substituted derivatives of 4′-O-demethylpodophyllotoxin were designed by aldehydes reacting with 4′-O-demethylpodophyllotoxin. Their cytotoxicity against cancer cell lines (HeLa) was evaluated using the MTT assay. Compounds 7a–7d, 7f, 7g, and 7h exhibited pronounced stronger activity than that of the positive control etoposide (VP-16). 4β-N-Substituted derivatives of 4′-O-demethylpodophyllotoxin were worthy of further study with potential antitumor activity.

  通过醛类与4′-O-去甲基鬼臼毒素反应，设计了10种4′-O-去甲基鬼臼毒素的4β-N-取代衍生物。使用MTT法评估了它们对癌细胞系（HeLa）的细胞毒性。化合物7a-7d、7f、7g和7h表现出比阳性对照依托泊苷（VP-16）更强的活性。4′-O-去甲基鬼臼毒素的4β-N-取代衍生物具有潜在的抗肿瘤活性，值得进一步研究。