Department of Chemistry, Faculty of Science, Yazd University, Yazd, 89195-741, Iran.
Department of Chemistry, Faculty of Science, Yazd University, Yazd, 89195-741, Iran.
Enzyme Microb Technol. 2019 Feb;121:29-36. doi: 10.1016/j.enzmictec.2018.11.002. Epub 2018 Nov 2.
Xanthine oxidase (XO) catalyzes the oxidation of xanthine to uric acid. Over-production of uric acid is a risk factor for hyperuricemia and other diseases. Although allopurinol decreases uric acid levels, it causes severe adverse effects. Therefore, more effort is needed in finding novel XO inhibitors with fewer side effects. In this study, differential pulse voltammetry was used to investigate the inhibitory effect of thymoquinone (TQ) on the XO activity while the major problem was the overlap of the obtained signals. Thus, Parallel Factor Analysis (PARAFAC) was applied to extract the useful information. Also, docking was used to investigate how TQ and the active site of XO fit together. PARAFAC results based on the voltammetry studies revealed that TQ blocks the catalytic centers of XO, which leads to a decrease in the electrochemical signal of Mo center in XO. The results also indicated the dose-dependent inhibition of XO with TQ. Molecular docking studies were shown TQ surrounds the active sites of XO and reduces the oxidation of xanthine to uric acid. Therefore, the electrochemical response of Mo decreases in the presence of TQ. This finding is in good agreement with the results obtained from molecular docking studies.
黄嘌呤氧化酶 (XO) 催化黄嘌呤氧化为尿酸。尿酸生成过多是高尿酸血症和其他疾病的一个危险因素。虽然别嘌醇能降低尿酸水平，但它会引起严重的不良反应。因此，需要更多的努力来寻找具有较少副作用的新型 XO 抑制剂。在这项研究中，采用差分脉冲伏安法研究了百里醌 (TQ) 对 XO 活性的抑制作用，而主要问题是获得的信号重叠。因此，平行因子分析 (PARAFAC) 被应用于提取有用信息。此外，对接还用于研究 TQ 和 XO 的活性位点如何结合在一起。基于伏安法研究的 PARAFAC 结果表明，TQ 阻断了 XO 的催化中心，导致 XO 中 Mo 中心的电化学信号降低。结果还表明，TQ 对 XO 的抑制作用呈剂量依赖性。分子对接研究表明，TQ 包围了 XO 的活性位点，减少了黄嘌呤向尿酸的氧化。因此，在 TQ 的存在下，Mo 的电化学响应降低。这一发现与分子对接研究的结果非常吻合。
