(1E,4E)-1-(3,4,5-trimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (1E,4E)-1-(3,4,5-trimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one
• 化学式: C₂₁H₂₄N₂O₄
• 分子量: 368.433
• InChiKey: NBGMGBHHJLPPOH-XBLVEGMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  70.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  川芎嗪 在 三氟化硼乙醚 、 双氧水 、 溶剂黄146 、 2-碘酰基苯甲酸 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 为溶剂， 反应 10.5h， 生成 (1E,4E)-1-(3,4,5-trimethoxyphenyl)-5-(3,5,6-trimethylpyrazin-2-yl)penta-1,4-dien-3-one
  参考文献：
  名称：

  Discovery of New Monocarbonyl Ligustrazine–Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer

  摘要：

  The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little, effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-kappa B, AKT, and ERK signaling, P-gp-mediated efflux of rhodamilie 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.

  DOI：

  10.1021/acs.jmedchem.5b01203

文献信息

• Discovery of New Monocarbonyl Ligustrazine–Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer
  作者：Yong Ai、Bin Zhu、Caiping Ren、Fenghua Kang、Jinlong Li、Zhangjian Huang、Yisheng Lai、Sixun Peng、Ke Ding、Jide Tian、Yihua Zhang

  DOI：10.1021/acs.jmedchem.5b01203

  日期：2016.3.10

  The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little, effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-kappa B, AKT, and ERK signaling, P-gp-mediated efflux of rhodamilie 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.