(1S,4aR,5S,6S,6aR,9S,11aS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate

• 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,4aR,5S,6S,6aR,9S,11aS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
• 英文别名: [(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] 1-(4-methoxyphenyl)triazole-4-carboxylate
• 化学式: C₃₀H₃₅N₃O₈
• 分子量: 565.623
• InChiKey: HJFAGGZZQIDXEA-RVPZNXJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-叠氮基-4-甲氧基苯 在 4-二甲氨基吡啶 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 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 、 水 、 叔丁醇 为溶剂， 反应 19.0h， 生成 (1S,4aR,5S,6S,6aR,9S,11aS,14R)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway

  摘要：

  A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 mu M) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 mu M) and 5-Fu (IC50 = 24.80 mu M) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.04.005

文献信息

• Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway
  作者：Qing-Kun Shen、Hao Deng、Shi-Ben Wang、Yu-Shun Tian、Zhe-Shan Quan

  DOI：10.1016/j.ejmech.2019.04.005

  日期：2019.7

  A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 mu M) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 mu M) and 5-Fu (IC50 = 24.80 mu M) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent. (C) 2019 Elsevier Masson SAS. All rights reserved.