(S)-2-methyl-butyric acid (S)-(3S,7S,8S,8aR)-8-[(3R,5R)-6-hydroxycarbamoyl-3-(4-chlorobenzoyloxy)-5-dihydroxy-hexyl]-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

• 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: (S)-2-methyl-butyric acid (S)-(3S,7S,8S,8aR)-8-[(3R,5R)-6-hydroxycarbamoyl-3-(4-chlorobenzoyloxy)-5-dihydroxy-hexyl]-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
• 英文别名: [(3S,5R)-7-[(1S,2S,6R,8S,8aR)-2,6-dimethyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-5-hydroxy-1-(hydroxyamino)-1-oxoheptan-3-yl] 4-chlorobenzoate
• 化学式: C₃₁H₄₂ClNO₇
• 分子量: 576.13
• InChiKey: JGNIPIZDJPIFIQ-GDLFHZQSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(4-chlorobenzoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 在 羟胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以64%的产率得到(S)-2-methyl-butyric acid (S)-(3S,7S,8S,8aR)-8-[(3R,5R)-6-hydroxycarbamoyl-3-(4-chlorobenzoyloxy)-5-dihydroxy-hexyl]-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species

  摘要：

  Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 mu M had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.005

文献信息

• Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species
  作者：Ruo-Kai Lin、Yuh-Feng Lin、Ming-Jen Hsu、Chang-Lin Hsieh、Chen-Yu Wang、Chih-Chiang Huang、Wei-Jan Huang

  DOI：10.1016/j.bmcl.2016.10.005

  日期：2016.11

  Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 mu M had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation. (C) 2016 Elsevier Ltd. All rights reserved.