(1S,5S,6S,6aR,9S,11aS,11bS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 4-cyanobenzoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,5S,6S,6aR,9S,11aS,11bS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 4-cyanobenzoate
• 英文别名: ent-1α-hydroxy-6β,7β-dihydroxy-[14β-O-(p-cyanobenzoic acid)]-15-oxo-7,20-oxo bridge-16-kaurene；[(1S,2S,5S,8R,9S,10S,11R,15S,18R)-9,10,15-trihydroxy-12,12-dimethyl-6-methylidene-7-oxo-17-oxapentacyclo[7.6.2.15,8.01,11.02,8]octadecan-18-yl] 4-cyanobenzoate
• 化学式: C₂₈H₃₁NO₇
• 分子量: 493.557
• InChiKey: YTFGGKQQBDABSR-LCYAIMSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  冬凌草甲素 、 对氰基苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到(1S,5S,6S,6aR,9S,11aS,11bS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 4-cyanobenzoate
  参考文献：
  名称：

  Oridonin derivatives as potential anticancer drug candidates triggering apoptosis through mitochondrial pathway in the liver cancer cells

  摘要：

  The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to enlarge the applied range of oridonin and explore its mechanism of action, a series of derivatives were designed and synthesized based on the structure of oridonin. Some of the derivatives were significantly more potent than oridonin against four cancer cell lines. Especially, the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly differentiated PLC/PRF/5 cells, with IC50 values as low as 1.36 mu M and 0.78 mu M respectively, while the IC50 values of oridonin are 8.12 mu M and 7.41 mu M. We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase. Moreover, it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins. Furthermore, compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect. Altogether, these results indicated that compound 20 is a promising lead for liver cancer therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.006

文献信息

• Oridonin derivatives as potential anticancer drug candidates triggering apoptosis through mitochondrial pathway in the liver cancer cells
  作者：Dongdong Luo、Yujiao Yi、Kai Peng、Tangrong Liu、Jiayu Yang、Shan Liu、Wanzhou Zhao、Xianjun Qu、Wengong Yu、Yuchao Gu、Shengbiao Wan

  DOI：10.1016/j.ejmech.2019.06.006

  日期：2019.9

  The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to enlarge the applied range of oridonin and explore its mechanism of action, a series of derivatives were designed and synthesized based on the structure of oridonin. Some of the derivatives were significantly more potent than oridonin against four cancer cell lines. Especially, the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly differentiated PLC/PRF/5 cells, with IC50 values as low as 1.36 mu M and 0.78 mu M respectively, while the IC50 values of oridonin are 8.12 mu M and 7.41 mu M. We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase. Moreover, it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins. Furthermore, compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect. Altogether, these results indicated that compound 20 is a promising lead for liver cancer therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.