ABSTRACT 5-Lipoxygenase (5-LO) is one of the key enzymes involved in the production of pro-inflammatory mediators, such as leukotriene B4 and cysteinyl leukotrienes. Inhibition of 5-LO is a promising therapeutic strategy against inflammation. Chalcones and flavones are known to have a broad spectrum of biological activities which include anti-inflammation, anti-fungal, anti-cancer, and anti-oxidant properties. In this work, computational approaches were used to screen chalcone and flavone derivatives for their potential as inhibitors of 5-LO. The scaffolds for chalcone and flavones were designed and used to select only chalcone and flavone compounds from the ASINEX database. Prior to docking, chalcone and flavone derivatives were filtered using Lipinski’s rule of five (ro5). The top-ranked hits from GLIDE were re-docked using GOLD software to validate the binding mode of the compounds which were screened. Six compounds were selected for further analysis for ADME properties, followed by molecular dynamic (MD) simulations in order to investigate binding interactions. Compound 6 (BAS00795786) had the highest potential as an inhibitor of 5-LO among the selected compounds.

中文翻译：

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查耳酮和黄酮衍生物作为 5-脂加氧酶 (5-LO) 抑制剂的虚拟筛选、ADME 研究和分子动力学模拟

摘要 5-脂氧合酶 (5-LO) 是参与促炎介质产生的关键酶之一，如白三烯 B4 和半胱氨酰白三烯。抑制 5-LO 是一种很有前景的炎症治疗策略。已知查耳酮和黄酮具有广谱的生物活性，包括抗炎、抗真菌、抗癌和抗氧化特性。在这项工作中，计算方法用于筛选查尔酮和黄酮衍生物作为 5-LO 抑制剂的潜力。查耳酮和黄酮的支架设计用于仅从 ASINEX 数据库中选择查耳酮和黄酮化合物。在对接之前，查尔酮和黄酮衍生物使用 Lipinski 的五法则 (ro5) 进行过滤。使用 GOLD 软件重新对接来自 GLIDE 的排名靠前的命中，以验证所筛选化合物的结合模式。选择了六种化合物进行 ADME 特性的进一步分析，然后进行分子动力学 (MD) 模拟以研究结合相互作用。在所选化合物中，化合物 6 (BAS00795786) 作为 5-LO 抑制剂的潜力最大。