Synthetic drugs such as allopurinol and benzbroarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase (XO) and cyclooxygenase 2 (COX-2) enzymes. In this study, we report the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2,092 flavonoids) using the iGEMDOCK software tool against the XO and COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of XO and COX-2. Myricetin and luteolin were found to be the potential dual inhibitors of XO and COX-2 as demonstrated by IC50: 62.7 and 3.29μg/mL (XO) / 70.8 and 16.38μg/mL (COX-2), respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of XO and COX-2 were discussed, which is expected for further rational drug design.

中文翻译：

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黄酮类化合物和异黄酮类植物化学抑制剂对黄嘌呤氧化酶和环氧合酶2的虚拟和体外生物测定筛选，用于治疗痛风

别嘌醇和苯溴隆等合成药物通常用于治疗痛风的复杂发病机制，痛风是一种由尿酸沉淀引起的关节炎症引起的代谢性疾病。我们试图通过靶向黄嘌呤氧化酶 (XO) 和环氧合酶 2 (COX-2) 酶来发现可以治疗痛风的新型植物化学物质。在本研究中，我们使用 iGEMDOCK 软件工具从 ZINC 和 PubChem 数据库（包含 2,092 种黄酮类化合物）中报告了针对 XO 和 COX-2 3D 蛋白质结构的 9 种黄酮类化合物的筛选。每种化合物还通过体外评估生物测定测试 XO 和 COX-2 的抑制作用。杨梅素和木犀草素被发现是 XO 和 COX-2 的潜在双重抑制剂，IC50 分别为：62.7 和 3.29μg/mL (XO) / 70.8 和 16.38μg/mL (COX-2)。此外，还讨论了黄酮类化合物与XO和COX-2活性位点结合的构效关系等重要因素，以期为进一步合理的药物设计提供参考。