3α-hydroxy-ent-labda-8(17),13E-dien-15-oic acid | 37886-47-8

• 物质功能分类: 天然产物 - 萜类
• 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: 3α-hydroxy-ent-labda-8(17),13E-dien-15-oic acid
• 英文别名: (2E)-5-[(1S,4aR,6S,8aR)-6-Hydroxy-5,5,8a-trimethyl-2-methylenedec ahydro-1-naphthalenyl]-3-methyl-2-pentenoic acid；3β-hydroxyanticopalic acid；3-hydroxycopalic acid；3-HCA
• CAS: 37886-47-8；63399-38-2；74559-97-0；84711-18-2；86363-30-6；103190-27-8
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: LNWOKEZJIRLIDO-BMASWZOASA-N

物化性质

• 沸点：
  454.5±45.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3α-hydroxy-ent-labda-8(17),13E-dien-15-oic acid 、 布洛芬 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以94%的产率得到3-ibuprofenylcopalic acid
  参考文献：
  名称：

  Synthesis, Characterization and in vitro, in vivo and in silico Anti-Inflammatory Studies of the Novel Hybrid Based on Ibuprofen and 3-Hydroxy-Copalic Acid Isolated from Copaiba Oil (Copaifera multijuga)

  摘要：

  A novel anti-inflammatory hybrid 3-ibuprofenyl-copalic acid (3-IbuCA) was synthesized from 3-hydroxy-copalic acid isolated from Amazonian copaiba oil (Copaifera multijuga Hayne). and the anti-inflammatory ibuprofen. After full characterization, several assays to verify its anti-inflammatory effects were performed in vitro, in vivo and in silico (molecular docking). Induced fit docking was performed to observe the interactions with the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). In vitro tests of cytotoxicity and tumor necrosis factor (TNF)-alpha inhibition, and in vivo tests of pleurisy, protein expression and gastrocytotoxicity were performed. Molecular docking studies with COX-1 and 2 showed binding free energies (Delta G) of -2.2 and -7.8 kcal mol(-1), respectively, while for mofezolac and indometbacin, the binding free energies AG presented values of -8.5 and -10.1 kcal mol(-1), which makes 3-IbuCA selective for COX-2 inhibition. This hybrid showed no toxicity against human macrophage at concentrations up to 2 mu M, and inhibited TNF-alpha production in lipopolysaccharide (LPS)-stimulated macrophages. In the pleurisy assays, 3-IbuCA reduced the total leukocytes and mononuclear cells, which was followed by reduction of p-IKB alpha (phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) protein expression. Compared with ibuprofen alone, the hybrid caused less gastric damage. Thus, the docking, together with in vitro and in vivo studies suggest that this novel hybrid has potential as a new anti-inflammatory agent.

  DOI：

  10.21577/0103-5053.20190266