6-((3E,5E,7E,9E)-10-(3-chloro-1H-pyrrol-2-yl)deca-3,5,7,9-tetraen-3-yl)-4-methoxy-3-methyl-2H-pyran-2-one | 1255529-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 6-((3E,5E,7E,9E)-10-(3-chloro-1H-pyrrol-2-yl)deca-3,5,7,9-tetraen-3-yl)-4-methoxy-3-methyl-2H-pyran-2-one
• 英文别名: 6-[(3E,5E,7E,9E)-10-(3-chloro-1H-pyrrol-2-yl)deca-3,5,7,9-tetraen-3-yl]-4-methoxy-3-methylpyran-2-one
• CAS: 1255529-10-2
• 化学式: C₂₁H₂₂ClNO₃
• 分子量: 371.864
• InChiKey: AYMLQLBNMFNRCM-ZBGTWWAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-methoxy-3,6-dimethyl-2H-pyran-2-one 在 N-甲基吡咯烷酮 、 selenium(IV) oxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 亚磷酸氢二甲酯 、 三苯胂 、 四丁基氟化铵 、 戴斯-马丁氧化剂 、 三乙胺 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.17h， 生成 6-((3E,5E,7E,9Z)-10-(3-chloro-1H-pyrrol-2-yl)deca-3,5,7,9-tetraen-3-yl)-4-methoxy-3-methyl-2H-pyran-2-one 、 6-((3E,5E,7E,9E)-10-(3-chloro-1H-pyrrol-2-yl)deca-3,5,7,9-tetraen-3-yl)-4-methoxy-3-methyl-2H-pyran-2-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Polyenylpyrrole Derivatives as Anticancer Agents Acting through Caspases-Dependent Apoptosis

  摘要：

  A class of polyenylpyrroles and their analogues were designed from a hit compound identified in a fungus. The compounds synthesized were evaluated for their cell cytotoxicity against human non-small-cell lung carcinoma cell lines A549. Two compounds were found to exhibit high cytotoxicity against A549 cells with IC50 of 0.6 and 0.01 mu M, respectively. The underlying mechanisms for the anticancer activity were demonstrated as caspases activation dependent apoptosis induction through loss of mitochondrial membrane potential, release of cytochrome c, increase in B-cell lymphoma-2-associated X protein (Bax) level, and decrease in B-cell lymphoma-2 (Bcl-2) level. The two compounds were nontoxic to normal human lung Beas-2b cells (IC50 > 80 mu M), indicating that they are highly selective in their cytotoxicity activities. Furthermore, one compound showed in vivo anticancer activity in human-lung-cancer-cell-bearing mice. These results open promising insights on how these conjugated polyenes mediate cytotoxicity and may provide a molecular rationale for future therapeutic interventions in carcinogenesis.

  DOI：

  10.1021/jm100619x

文献信息

• Synthesis and Biological Evaluation of Polyenylpyrrole Derivatives as Anticancer Agents Acting through Caspases-Dependent Apoptosis
  作者：Zhanxiong Fang、Pei-Chun Liao、Yu-Liang Yang、Feng-Ling Yang、Yi-Lin Chen、Yulin Lam、Kuo-Feng Hua、Shih-Hsiung Wu

  DOI：10.1021/jm100619x

  日期：2010.11.25

  A class of polyenylpyrroles and their analogues were designed from a hit compound identified in a fungus. The compounds synthesized were evaluated for their cell cytotoxicity against human non-small-cell lung carcinoma cell lines A549. Two compounds were found to exhibit high cytotoxicity against A549 cells with IC50 of 0.6 and 0.01 mu M, respectively. The underlying mechanisms for the anticancer activity were demonstrated as caspases activation dependent apoptosis induction through loss of mitochondrial membrane potential, release of cytochrome c, increase in B-cell lymphoma-2-associated X protein (Bax) level, and decrease in B-cell lymphoma-2 (Bcl-2) level. The two compounds were nontoxic to normal human lung Beas-2b cells (IC50 > 80 mu M), indicating that they are highly selective in their cytotoxicity activities. Furthermore, one compound showed in vivo anticancer activity in human-lung-cancer-cell-bearing mice. These results open promising insights on how these conjugated polyenes mediate cytotoxicity and may provide a molecular rationale for future therapeutic interventions in carcinogenesis.