3β,16β-dihydroxy-17α-H-18β-H-28-norolean-12-ene

• 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: 3β,16β-dihydroxy-17α-H-18β-H-28-norolean-12-ene
• 英文别名: (3S,4aR,6aR,6bS,8S,8aR,12aR,14aR,14bR)-4,4,6a,6b,11,11,14b-heptamethyl-2,3,4a,5,6,7,8,8a,9,10,12,12a,14,14a-tetradecahydro-1H-picene-3,8-diol
• 化学式: C₂₉H₄₈O₂
• 分子量: 428.699
• InChiKey: XOHQCIXQYXPLIO-YJQNGITKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  31
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  刺囊酸 在 cobalt(II) chloride hexahydrate 、 硫酸 、 dipyridine chromium(VI) oxide 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 10.17h， 生成 3β,16β-dihydroxy-17α-H-18β-H-28-norolean-12-ene 、 3β,16α-dihydroxy-17α-H-18β-H-28-norolean-12-ene
  参考文献：
  名称：

  Discovery and structure-activity relationship of auriculatone: A potent hepatoprotective agent against acetaminophen-induced liver injury

  摘要：

  Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10 mu M. Structure activity relationship on auriculatone and its analogs showed that absence of the C17 carboxyl group of auriculatone was essential to achieve good hepatoprotective activity, and that the C3-OH, C16 carbonyl and C12-C13 olefinic group were critical for retaining the exceptional activity of auriculatone. Any modifications in the current investigation were all detrimental to the hepatoprotective activity. Docking and drug-metabolizing activity studies demonstrated that CYP3A4 was likely the main target of auriculatone, and that auriculatone elicited the hepatoprotective effect possibly through inhibiting CYP3A4's metabolism of APAP to the toxic metabolite NAPQI. The work may pave the way for the use of auriculatone in the treatment of APAP-induced liver injury. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.07.028

文献信息

• Discovery and structure-activity relationship of auriculatone: A potent hepatoprotective agent against acetaminophen-induced liver injury
  作者：Meng Zhou、Min Wang、Rui-Feng Zhong、Xiang-Ming Liao、Lian-Li Deng、Guo-Bo Xu、Xun He、Jing Li、Yong-Jun Li、Ting Liu、Yong-Lin Wang、Shang-Gao Liao

  DOI：10.1016/j.bmcl.2017.07.028

  日期：2017.8

  Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10 mu M. Structure activity relationship on auriculatone and its analogs showed that absence of the C17 carboxyl group of auriculatone was essential to achieve good hepatoprotective activity, and that the C3-OH, C16 carbonyl and C12-C13 olefinic group were critical for retaining the exceptional activity of auriculatone. Any modifications in the current investigation were all detrimental to the hepatoprotective activity. Docking and drug-metabolizing activity studies demonstrated that CYP3A4 was likely the main target of auriculatone, and that auriculatone elicited the hepatoprotective effect possibly through inhibiting CYP3A4's metabolism of APAP to the toxic metabolite NAPQI. The work may pave the way for the use of auriculatone in the treatment of APAP-induced liver injury. (C) 2017 Elsevier Ltd. All rights reserved.