Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
School of Pharmacy, University of Thessaloniki, 54124 Thessaloniki, Greece.
Molecules. 2021 Jan 27;26(3):659. doi: 10.3390/molecules26030659.
Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects.
Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock.
All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis.
A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.
炎症是一种由受损细胞释放化学介质引发的对有害刺激的复杂反应。花生四烯酸的代谢产物，由环加氧酶和脂加氧酶作用产生，在这个过程中发挥重要作用。几种非甾体抗炎药作为环加氧酶抑制剂。然而，几乎所有这些药物都有不良的副作用。
使用 PASS 程序预测化合物的抗炎作用。通过角叉菜胶足肿胀试验评估抗炎活性。分别使用绵羊 COX-1、人重组 COX-2 和大豆 LOX-1 测试 COX 和 LOX 的抑制作用。使用 Autodock 进行对接分析。
所有设计的衍生物根据 PASS 都有很好的预测结果，并进行了合成和实验评估。这些化合物表现出体内抗炎作用，其中 11 种与吲哚美辛相当或更好。尽管其中一些对 COX-1/2 或 LOX 没有或低抑制作用，但某些化合物的 COX-1 抑制作用明显高于萘普生，COX-2 抑制作用也很好，这可以通过对接分析得到解释。
获得了一些具有良好抗炎作用的化合物。尽管某些化合物表现出显著的 COX 抑制作用，但这种作用并不符合抗炎结果，表明存在其他机制。
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