4β-[methyl-3-(sulfonamido)thiophene-2-carboxylate]podophyllotoxin | 1365699-69-9

• 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: 4β-[methyl-3-(sulfonamido)thiophene-2-carboxylate]podophyllotoxin
• 英文别名: methyl 3-[[(5S,5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]sulfamoyl]thiophene-2-carboxylate
• CAS: 1365699-69-9
• 化学式: C₂₈H₂₇NO₁₁S₂
• 分子量: 617.654
• InChiKey: ARSZMSABYRDJJH-CPUMGYLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  182
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  3-氯磺酰基-2-噻吩甲酸甲酯 、 4β-amino-4-deoxypodophyllotoxin 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到4β-[methyl-3-(sulfonamido)thiophene-2-carboxylate]podophyllotoxin
  参考文献：
  名称：

  Synthesis and biological evaluation of 4β-sulphonamido and 4β-[(4′-sulphonamido)benzamide]podophyllotoxins as DNA topoisomerase-IIα and apoptosis inducing agents

  摘要：

  A series of new 4 beta-sulphonamido and 4 beta-[(4'-sulphonamido)benzamide] conjugates of podophyllotoxin (11a-j and 15a-g) were synthesized and evaluated for anticancer activity against six human cancer cell lines and found to be more potent than etoposide. Some of the compounds 11b, 11d and 11e that showed significant antiproliferative activity in Colo-205 cells, were superior to etoposide. The flow cytometric analysis indicates that these compounds (11b, 11d and 11e) showed G2/M cell cycle arrest and among them 11e is the most effective. It is observed that this compound (11e) caused both single-strand DNA breaks as observed by comet assay as well as double-strand DNA breaks as indicated by gamma-H2AX. Further 11e showed inhibition of topo-II alpha as observed from Western blot analysis and related studies. Compounds caused activation of ATM as well as Chk1 protein indicating that the compound caused effective DNA damage. Moreover activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein suggests that this compound (11e) has apoptotic cell death inducing ability, apart from acting as a topo-II alpha inhibitor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.039

文献信息

• Synthesis and biological evaluation of 4β-sulphonamido and 4β-[(4′-sulphonamido)benzamide]podophyllotoxins as DNA topoisomerase-IIα and apoptosis inducing agents
  作者：Ahmed Kamal、Paidakula Suresh、M. Janaki Ramaiah、Adla Mallareddy、Syed Imthiajali、S.N.C.V.L. Pushpavalli、A. Lavanya、Manika Pal-Bhadra

  DOI：10.1016/j.bmc.2012.01.039

  日期：2012.3

  A series of new 4 beta-sulphonamido and 4 beta-[(4'-sulphonamido)benzamide] conjugates of podophyllotoxin (11a-j and 15a-g) were synthesized and evaluated for anticancer activity against six human cancer cell lines and found to be more potent than etoposide. Some of the compounds 11b, 11d and 11e that showed significant antiproliferative activity in Colo-205 cells, were superior to etoposide. The flow cytometric analysis indicates that these compounds (11b, 11d and 11e) showed G2/M cell cycle arrest and among them 11e is the most effective. It is observed that this compound (11e) caused both single-strand DNA breaks as observed by comet assay as well as double-strand DNA breaks as indicated by gamma-H2AX. Further 11e showed inhibition of topo-II alpha as observed from Western blot analysis and related studies. Compounds caused activation of ATM as well as Chk1 protein indicating that the compound caused effective DNA damage. Moreover activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein suggests that this compound (11e) has apoptotic cell death inducing ability, apart from acting as a topo-II alpha inhibitor. (C) 2012 Elsevier Ltd. All rights reserved.