(5R,6R)-methyl 7-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: (5R,6R)-methyl 7-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate
• 英文别名: methyl (7R,8R)-6-(6-methyl-1H-benzimidazol-2-yl)-8-(3,4,5-trimethoxyphenyl)-7,8-dihydrobenzo[f][1,3]benzodioxole-7-carboxylate
• 化学式: C₃₀H₂₈N₂O₇
• 分子量: 528.562
• InChiKey: BVJLOBBMQKYTQC-SXOMAYOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (5R,6R,7R)-methyl 7-(hydroxymethyl)-8-oxo-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate 在 sodium metabisulfite 、 sodium tetrahydroborate 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.5h， 生成 (5R,6R)-methyl 7-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors

  摘要：

  A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 μM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.

  DOI：

  10.1016/j.bmc.2014.07.031

文献信息

• Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors
  作者：Ahmed Kamal、T. Srinivasa Reddy、Sowjanya Polepalli、Nekkanti Shalini、V. Ganga Reddy、A.V. Subba Rao、Nishant Jain、Nagula Shankaraiah

  DOI：10.1016/j.bmc.2014.07.031

  日期：2014.10

  A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 μM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.