ridaifen-SB8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ridaifen-SB8
• 英文别名: 1-[2-[4-[1-[4-(2-Pyrrolidin-1-ylethoxy)phenyl]pent-1-enyl]phenoxy]ethyl]pyrrolidine；1-[2-[4-[1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]pent-1-enyl]phenoxy]ethyl]pyrrolidine
• 化学式: C₂₉H₄₀N₂O₂
• 分子量: 448.649
• InChiKey: LKEYSUQAZPGMFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,4'-二羟基二苯甲酮 在 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 paraffin oil 、 苯 为溶剂， 反应 32.75h， 生成 ridaifen-SB8
  参考文献：
  名称：

  Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen species-dependent signaling pathway

  摘要：

  Tamoxifen is an anticancer agent widely used for treatment of estrogen receptor (ER alpha)-positive breast cancer. We previously developed a novel synthesis of tamoxifen and its derivatives, named Ridaifens (RIDS). Some of them, including RID-SB8, exhibited a stronger anticancer activity than tamoxifen in ER alpha-positive MCF-7 cells while having lost the affinity for ER alpha, suggesting an ER alpha-independent anticancer mode of action. In this study, we investigated the underlying mechanism by which RID-SB8 exerts anticancer activity. As expected, anticancer activity of RID-SB8 was not influenced upon knockdown of ER alpha expression in MCF-7 cells. RID-SB8 exerted similar anticancer effects on thirteen ER alpha-negative cancer cell lines including human gliosarcoma SF539 cells. In SF539 cells, RID-SB8 triggered loss of mitochondrial membrane potential (Delta Psi(m)) and progression of apoptosis accompanied by activation of caspases and translocation of apoptosis-inducing factor (AIF) to the nucleus. Furthermore, it induced reactive oxygen species (ROS), and a ROS scavenger, N-acetylcysteine (NAC), canceled loss of Delta Psi(m) and progression of apoptosis triggered by RID-SB8. Using fifteen human cancer cell lines, we demonstrated a significant correlation between RID-SB8 concentration required for ROS production and that required for cytotoxic effect across these cell lines, but such correlation was not observed for tamoxifen. Finally, the selective induction of ROS and cytotoxic effect on cancer cells by RID-SB8 were confirmed. From these results, we concluded that RID-SB8 exerts an anticancer effect via a mode of action distinct from tamoxifen, and that RID-SB8 could become a promising anticancer lead compound which selectively induces ROS formation and apoptosis in cancer cells. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2013.08.020