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首页> 外文期刊>Journal of the Brazilian Chemical Society >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)
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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)

机译：基于西堡石油（Copaifera Multijuga）的布洛芬和3-羟基 - 共酸的新型杂交种和硅抗炎研究的合成，表征和体内硅抗炎研究

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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)-α 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 (ΔG) of -2.2 and -7.8 kcal mol-1, respectively, while for mofezolac and indomethacin, the binding free energies ΔG 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 ?μM, and inhibited TNF-α 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-IKBα (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.
机译：用从亚马逊椰子油（Copaifera Multijuga Hayne）分离的3-羟基 - 共酸合成了一种新的抗炎杂交3-离氨基戊基 - 共酸（3-Ibuca），以及抗炎布洛芬。在完全表征之后，在体内和硅（分子对接）中在体外进行几种测定以验证其抗炎作用。进行诱导的配合对接以观察与酶环氧化酶-1（COX-1）和环氧化酶-2（COX-2）的相互作用。进行细胞毒性和肿瘤坏死因子（TNF）-α抑制的体外试验，并进行胸膜炎，蛋白质表达和胃毒性的体内试验。用COX-1和2的分子对接研究分别显示出-2.2和-7.8kcal-1的无结合能量（Δg），而对于Mofezolac和Indomethacin，其具有-8.5和-10.1kcalΔg呈现的无粘合能量ΔgΔg -1，这使3-Ibuca选择性用于COX-2抑制。该杂种在高达2μm的浓度下对人巨噬细胞没有毒性，并抑制脂多糖（LPS）刺激的巨噬细胞的TNF-α产生。在血浆测定中，3-Ibuca降低了总白细胞和单核细胞，然后进行了对P-IKBα的降低（Kappa轻微多肽基因增强剂的磷酸化核因子，B细胞抑制剂，α）蛋白表达。与单独的布洛芬相比，杂交造成胃损伤较少。因此，对接，与体外和体内研究一起表明这种新型杂交物具有新的抗炎剂。

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