4β-[6-(3,4-dihydro-2-methyl-3-(4-fluorophenyl)-4-oxoquinazolin-6-yloxy)hexanamido]-4-desoxypodophyllotoxin

• 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-[6-(3,4-dihydro-2-methyl-3-(4-fluorophenyl)-4-oxoquinazolin-6-yloxy)hexanamido]-4-desoxypodophyllotoxin
• 英文别名: N-[(5S,5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]-6-[3-(4-fluorophenyl)-2-methyl-4-oxoquinazolin-6-yl]oxyhexanamide
• 化学式: C₄₃H₄₂FN₃O₁₀
• 分子量: 779.819
• InChiKey: AHKLMSLWAFSCSE-KXICPUGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  57
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  6-溴己酰氯 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 4β-[6-(3,4-dihydro-2-methyl-3-(4-fluorophenyl)-4-oxoquinazolin-6-yloxy)hexanamido]-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Quinazolino linked 4β-amidopodophyllotoxin conjugates regulate angiogenic pathway and control breast cancer cell proliferation

  摘要：

  A series of new conjugates of quinazolino linked 4 beta-amidopodophyllotoxins 10aa-af and 10ba-bf were synthesized and evaluated for their anticancer activity against human pancreatic carcinoma (Panc-1) as well as breast cancer cell lines such as MCF-7 and MDA-MB-231 by employing MTT assay. Among these conjugates, some of them like 10bc, 10bd, 10be and 10bf exhibited high potency of cytotoxicity. Flow cytometric analysis showed that these conjugates arrested the cell cycle in the G2/M phase and caused the increase in expression of p53 and cyclin B1 protein with concomitant decrease in Cdk1 thereby suggesting the inhibitory action of these conjugates on mitosis. Interestingly, we observed a decrease in expression of proteins that control the tumor micro environment such as VEGF-A, STAT-3, ERK1/2, ERK-p, AKT-1 ser 473 phosphorylation in compounds treated breast cancer cells. Further, these effective conjugates have exhibited inhibitory action on integrin (alpha V beta III). Furthermore, the MCF-7 cells that were arrested and lost the proliferative capacity undergo mitochondrial mediated apoptosis by activation of caspases-9. Thus these conjugates have the potential to control breast cancer cell growth by effecting tumor angiogenesis and invasion. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.051

文献信息

• Quinazolino linked 4β-amidopodophyllotoxin conjugates regulate angiogenic pathway and control breast cancer cell proliferation
  作者：Ahmed Kamal、Jaki R. Tamboli、M. Janaki Ramaiah、S.F. Adil、S.N.C.V.L. Pushpavalli、Raksha Ganesh、Pranjal Sarma、Utpal Bhadra、Manika Pal-Bhadra

  DOI：10.1016/j.bmc.2013.08.051

  日期：2013.11

  A series of new conjugates of quinazolino linked 4 beta-amidopodophyllotoxins 10aa-af and 10ba-bf were synthesized and evaluated for their anticancer activity against human pancreatic carcinoma (Panc-1) as well as breast cancer cell lines such as MCF-7 and MDA-MB-231 by employing MTT assay. Among these conjugates, some of them like 10bc, 10bd, 10be and 10bf exhibited high potency of cytotoxicity. Flow cytometric analysis showed that these conjugates arrested the cell cycle in the G2/M phase and caused the increase in expression of p53 and cyclin B1 protein with concomitant decrease in Cdk1 thereby suggesting the inhibitory action of these conjugates on mitosis. Interestingly, we observed a decrease in expression of proteins that control the tumor micro environment such as VEGF-A, STAT-3, ERK1/2, ERK-p, AKT-1 ser 473 phosphorylation in compounds treated breast cancer cells. Further, these effective conjugates have exhibited inhibitory action on integrin (alpha V beta III). Furthermore, the MCF-7 cells that were arrested and lost the proliferative capacity undergo mitochondrial mediated apoptosis by activation of caspases-9. Thus these conjugates have the potential to control breast cancer cell growth by effecting tumor angiogenesis and invasion. (C) 2013 Elsevier Ltd. All rights reserved.