4'-demethyl-4-deoxypodophyllotoxin 4'-(p-nitrophenyl) carbonate | 1308813-97-9

• 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: 4'-demethyl-4-deoxypodophyllotoxin 4'-(p-nitrophenyl) carbonate
• 英文别名: [4-[(5R,5aR,8aR)-6-oxo-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate
• CAS: 1308813-97-9
• 化学式: C₂₈H₂₃NO₁₁
• 分子量: 549.491
• InChiKey: LJNJIQOPHSGYKL-CSKMKTBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  145
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 4'-demethyl-4-deoxypodophyllotoxin 4'-(p-nitrophenyl) carbonate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以68%的产率得到4'-demethyl-4-deoxypodophyllotoxin 4'-(4-methylpiperazine) carbamate
  参考文献：
  名称：

  Synthesis and biological evaluation of derivatives of 4-deoxypodophyllotoxin as antitumor agents

  摘要：

  In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p-nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC50 values were 0.102, 0.180 and 0.0195 mu M, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.004
• 作为产物：
  描述：

  去氧鬼臼毒素 在 吡啶 、 甲烷磺酸 、 sodium iodide 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 4'-demethyl-4-deoxypodophyllotoxin 4'-(p-nitrophenyl) carbonate
  参考文献：
  名称：

  Synthesis and biological evaluation of derivatives of 4-deoxypodophyllotoxin as antitumor agents

  摘要：

  In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p-nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC50 values were 0.102, 0.180 and 0.0195 mu M, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.004

文献信息

• Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects
  作者：Shi-Wu Chen、Yuan-Yu Gao、Ni-Ni Zhou、Jie Liu、Wen-Ting Huang、Ling Hui、Yan Jin、Yong-Xin Jin

  DOI：10.1016/j.bmcl.2011.10.024

  日期：2011.12

  In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4′-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4′-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities

  为了产生具有优良生物活性和降低的毒性的化合物，合成了12个氨基甲酸酯的4'-脱甲基-4-脱氧鬼臼毒素，N-（1-氧基-1'-脱甲基-4-4-脱氧鬼臼酸）-α-氨基酸酰胺。并评估其抗增殖活性和细胞周期效应。与母体DPT或抗癌药VP-16相比，这些合成的化合物被证明对四种细胞系（A-549，HeLa，SiHa和HL-60）具有更强的亲水性，以及改善的或相当的体外细胞毒性。此外，流式细胞仪分析表明，N-（1-氧基-1'-脱甲基-4-脱氧鬼臼酸）-d -α-次甲基酰胺（15f）诱导了A-549细胞在G2 / M期的细胞周期停滞。
• Synthesis of hybrid 4-deoxypodophyllotoxin–5-fluorouracil compounds that inhibit cellular migration and induce cell cycle arrest
  作者：Xiao-Wen Guan、Xiao-Hui Xu、Shi-Liang Feng、Zhen-Bo Tang、Shi-Wu Chen、Ling Hui

  DOI：10.1016/j.bmcl.2016.02.013

  日期：2016.3

  A series of deoxypodophyllotoxin-5-fluorouracil hybrid compounds were synthesized, and their cytotoxic activity was evaluated using four human cancer cell lines (HeLa, A549, HCT-8, and HepG2) and the human normal cell line WI-38. The synthesized compounds exhibited greater cytotoxic activity in tumor cells and reduced toxicity in the normal cell line compared with the anticancer drug VP-16 and 5-FU. Additionally, the most potent of these compounds-40-O-demethyl-4-deoxypodophyllotoxin-40-yl 4-((6-(2-(5-fluorouracil-yl) acetamido) hexyl) amino)-4-oxobutanoate (compound 22)-induced cell-cycle arrest in the G2/M phase by regulating levels of cdc2, cyclinB1, and p-cdc2 in A549 cells. Furthermore, compound 22 may inhibited the migration of A549 cells via down-regulation of MMP-9 and up-regulation of TIMP-1. (C) 2016 Elsevier Ltd. All rights reserved.