5-[4-[4-[[[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]amino]methyl]phenyl]triazol-1-yl]-N-hydroxypentanamide | 1360131-05-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 5-[4-[4-[[[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]amino]methyl]phenyl]triazol-1-yl]-N-hydroxypentanamide
• CAS: 1360131-05-0
• 化学式: C₄₁H₄₅N₅O₁₂
• 分子量: 799.835
• InChiKey: OBZKXYPZHKMZMG-WNRPIQNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  58
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  252
• 氢给体数：
  7
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  柔红霉素 盐酸盐 在 三氟化硼乙醚 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.5h， 生成 5-[4-[4-[[[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]amino]methyl]phenyl]triazol-1-yl]-N-hydroxypentanamide
  参考文献：
  名称：

  Dual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors

  摘要：

  Strategies to ameliorate the flaws of current chemotherapeutic agents, while maintaining potent anticancer activity, are of particular interest. Agents which can modulate multiple targets may have superior utility and fewer side effects than current single-target drugs. To explore the prospect in cancer therapy of a bivalent agent that combines two complementary chemo-active groups within a single molecular architecture, we have synthesized dual-acting histone deacetylase and topoisomerase II inhibitors. These dual-acting agents are derived from suberoylanilide hydroxamic acid (SAHA) and anthracycline daunorubicin, prototypical histone deacetylase (HDAC) and topoisomerase II (Topo II) inhibitors, respectively. We report herein that these agents present the signatures of inhibition of HDAC and Topo II in both cell-free and whole-cell assays. Moreover, these agents potently inhibit the proliferation of representative cancer cell lines.

  DOI：

  10.1021/jm200799p

文献信息

• Dual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors
  作者：William Guerrant、Vishal Patil、Joshua C. Canzoneri、Adegboyega K. Oyelere

  DOI：10.1021/jm200799p

  日期：2012.2.23

  Strategies to ameliorate the flaws of current chemotherapeutic agents, while maintaining potent anticancer activity, are of particular interest. Agents which can modulate multiple targets may have superior utility and fewer side effects than current single-target drugs. To explore the prospect in cancer therapy of a bivalent agent that combines two complementary chemo-active groups within a single molecular architecture, we have synthesized dual-acting histone deacetylase and topoisomerase II inhibitors. These dual-acting agents are derived from suberoylanilide hydroxamic acid (SAHA) and anthracycline daunorubicin, prototypical histone deacetylase (HDAC) and topoisomerase II (Topo II) inhibitors, respectively. We report herein that these agents present the signatures of inhibition of HDAC and Topo II in both cell-free and whole-cell assays. Moreover, these agents potently inhibit the proliferation of representative cancer cell lines.