9'-(2-methoxyphenyl)-noscapine | 1621072-66-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 邻苯二甲酸异喹啉类
• 英文名称: 9'-(2-methoxyphenyl)-noscapine
• 英文别名: (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-9-(2-methoxyphenyl)-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3H-2-benzofuran-1-one
• CAS: 1621072-66-9
• 化学式: C₂₉H₂₉NO₈
• 分子量: 519.551
• InChiKey: HDVWNBDSURGDIU-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  84.9
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-甲氧基苯基硼酸 、 9-bromonoscapine 在 potassium phosphate 、 palladium diacetate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以41%的产率得到9'-(2-methoxyphenyl)-noscapine
  参考文献：
  名称：

  Novel 9′-substituted-noscapines: Synthesis with Suzuki cross-coupling, structure elucidation and biological evaluation

  摘要：

  Tubulin is a major molecular target for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites on tubulin, usually its β-subunit. Among the antimitotic agents that perturb microtubule dynamics, noscapinoids represent an emerging class of agents. In particular, 9'-bromonoscapine (EM011) has been identified as a potent noscapine analog. Here we present high yielding, efficient synthetic methods based on Suzuki coupling of 9'-alkyl and 9'-arylnoscapines and an evaluation of their antiproliferative properties. Our results showed that 9'-alkyl and 9'-aryl derivatives inhibit proliferation of human cancer cells. The most active compounds were the 9'-methyl and the 9'-phenyl derivatives, which showed similar cytotoxic potency in comparison to the 9'-brominated derivative. Interestingly these newly synthesized derivatives did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. All of these derivatives, except 9'-(2-methoxyphenyl)-noscapine, efficiently induced a cell cycle arrest in the G2/M phase of the cell cycle in HeLa and Jurkat cells. Furthermore, we showed that the most active compounds in HeLa cells induced apoptosis following the mitochondrial pathway with the activation of both caspase-9 and caspase-3. In addition, these compounds significantly reduced the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2.

  DOI：

  10.1016/j.ejmech.2014.07.050

文献信息

• Novel 9′-substituted-noscapines: Synthesis with Suzuki cross-coupling, structure elucidation and biological evaluation
  作者：Elena Porcù、Attila Sipos、Giuseppe Basso、Ernest Hamel、Ruoli Bai、Verena Stempfer、Antal Udvardy、Attila Cs. Bényei、Helmut Schmidhammer、Sándor Antus、Giampietro Viola

  DOI：10.1016/j.ejmech.2014.07.050

  日期：2014.9

  Tubulin is a major molecular target for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites on tubulin, usually its β-subunit. Among the antimitotic agents that perturb microtubule dynamics, noscapinoids represent an emerging class of agents. In particular, 9'-bromonoscapine (EM011) has been identified as a potent noscapine analog. Here we present high yielding, efficient synthetic methods based on Suzuki coupling of 9'-alkyl and 9'-arylnoscapines and an evaluation of their antiproliferative properties. Our results showed that 9'-alkyl and 9'-aryl derivatives inhibit proliferation of human cancer cells. The most active compounds were the 9'-methyl and the 9'-phenyl derivatives, which showed similar cytotoxic potency in comparison to the 9'-brominated derivative. Interestingly these newly synthesized derivatives did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. All of these derivatives, except 9'-(2-methoxyphenyl)-noscapine, efficiently induced a cell cycle arrest in the G2/M phase of the cell cycle in HeLa and Jurkat cells. Furthermore, we showed that the most active compounds in HeLa cells induced apoptosis following the mitochondrial pathway with the activation of both caspase-9 and caspase-3. In addition, these compounds significantly reduced the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2.