N-(4'-ethoxyphenylcarbonyl)-4α-amino-19-nor-ent-13-hydroxykaur-16-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: N-(4'-ethoxyphenylcarbonyl)-4α-amino-19-nor-ent-13-hydroxykaur-16-ene
• 英文别名: 4-ethoxy-N-[(1R,4S,5R,9S,10R,13S)-13-hydroxy-5,9-dimethyl-14-methylidene-5-tetracyclo[11.2.1.01,10.04,9]hexadecanyl]benzamide
• 化学式: C₂₈H₃₉NO₃
• 分子量: 437.623
• InChiKey: WKZWYXXQHYTHMS-OJEPFFBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  甜叶菊甙元 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 三乙胺 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 7.17h， 生成 N-(4'-ethoxyphenylcarbonyl)-4α-amino-19-nor-ent-13-hydroxykaur-16-ene
  参考文献：
  名称：

  Synthesis of C-4-Substituted Steviol Derivatives and Their Inhibitory Effects against Hepatitis B Virus

  摘要：

  ent-13-Hydr oxykaur-16-en e-19-N-butylureide (6) was one of 33 synthesized C-4-substituted steviol derivatives that were evaluated for their effects on hepatitis B virus (HBV) surface antigen (HBsAg) secretion. The IC50 (16.9 mu M) and SI (57.7) values for inhibiting HBV DNA replication of compound 6 were greater than those of the reference compound, lamivudine (3-TC; IC50: 107.5 mu M; SI: 22.0). Thus, the anti-HBV mechanism of 6 was investigated, and it specifically inhibited viral gene expression and reduced viral DNA levels, as well as potently attenuated all of the viral promoter activity of HBV-expressing Huh7 cells. Examination of cellular signaling pathways found that 6 inhibited the activities of the nuclear factor (NF)-kappa B-and activator protein (AP)-1 element containing promoters, but had no effects on AP-2 or interferon-stimulated response element (ISRE)-containing promoters in HBV-expressing cells. Meanwhile, it significantly eliminated NF-kappa B and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling-related protean levels and inhibited their phosphorylation in HBV-transfected Huh? cells. The inhibitory potency of 6 against HBV DNA replication was reversed by cotransfecting the NF-kappa B p65 expression plasmid. Using the MAPK-specific activator anisomycin also reversed the inhibitory effect of 6 on viral DNA replication. The present findings suggest that the anti-HBV mechanism of 6 is partly mediated through the NP-kappa B and MAPK signaling pathways.

  DOI：

  10.1021/acs.jnatprod.6b00671

文献信息

• Synthesis of C-4-Substituted Steviol Derivatives and Their Inhibitory Effects against Hepatitis B Virus
  作者：Shwu-Jiuan Lin、Ta-Chi Su、Chin-Nan Chu、Yi-Chih Chang、Li-Ming Yang、Yu-Cheng Kuo、Tsurng-Juhn Huang

  DOI：10.1021/acs.jnatprod.6b00671

  日期：2016.12.23

  ent-13-Hydr oxykaur-16-en e-19-N-butylureide (6) was one of 33 synthesized C-4-substituted steviol derivatives that were evaluated for their effects on hepatitis B virus (HBV) surface antigen (HBsAg) secretion. The IC50 (16.9 mu M) and SI (57.7) values for inhibiting HBV DNA replication of compound 6 were greater than those of the reference compound, lamivudine (3-TC; IC50: 107.5 mu M; SI: 22.0). Thus, the anti-HBV mechanism of 6 was investigated, and it specifically inhibited viral gene expression and reduced viral DNA levels, as well as potently attenuated all of the viral promoter activity of HBV-expressing Huh7 cells. Examination of cellular signaling pathways found that 6 inhibited the activities of the nuclear factor (NF)-kappa B-and activator protein (AP)-1 element containing promoters, but had no effects on AP-2 or interferon-stimulated response element (ISRE)-containing promoters in HBV-expressing cells. Meanwhile, it significantly eliminated NF-kappa B and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling-related protean levels and inhibited their phosphorylation in HBV-transfected Huh? cells. The inhibitory potency of 6 against HBV DNA replication was reversed by cotransfecting the NF-kappa B p65 expression plasmid. Using the MAPK-specific activator anisomycin also reversed the inhibitory effect of 6 on viral DNA replication. The present findings suggest that the anti-HBV mechanism of 6 is partly mediated through the NP-kappa B and MAPK signaling pathways.