Background: Xanthine oxidase (XO; EC 1.17.3.2) has been considered as a potent drug target for the cure and management of pathological conditions prevailing due to high levels of uric acid in the bloodstream. The role of xanthine oxidase has been well established in the generation of hyperuricemia and gout due to its important role in catalytic oxidative hydroxylation of hypoxanthine to xanthine and further catalyses of xanthine to generate uric acid. In this research, syringic acid, a bioactive phenolic acid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase.

Objective: The study aimed to develop new xanthine oxidase inhibitors from natural constituents along with the antioxidant potential.

Methods: In this report, we designed and synthesized syringic acid derivatives hybridized with alcohol and amines to form ester and amide linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential.

Results: Results of the study revealed that SY3 produces very good xanthine oxidase inhibitory activity. All the compounds showed very good antioxidant activity. The enzyme kinetic studies performed on syringic acid derivatives showed a potential inhibitory effect on XO ability in a competitive manner with IC50 value ranging from 07.18μM-15.60μM and SY3 was revealed as the most active derivative. Molecular simulation revealed that new syringic acid derivatives interacted with the amino acid residues SER1080, PHE798, GLN1194, ARG912, GLN 767, ALA1078 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential.

Conclusion: Molecular docking proved to be an effective and selective tool in the design of new syringic acid derivatives .This hybridization of two natural constituents could lead to desirable xanthine oxidase inhibitors with improved activity.

背景：黄嘌呤氧化酶（XO； EC 1.17.3.2）被认为是治疗和治疗由于血液中尿酸水平较高而普遍存在的病理状况的有效药物靶标。黄嘌呤氧化酶在高尿酸血症和痛风的发生中已被很好地确立，这是由于其在次黄嘌呤向黄嘌呤的催化氧化羟基化以及进一步催化黄嘌呤催化生成尿酸中的重要作用。在这项研究中，对丁香酸（一种具有生物活性的酚酸）进行了研究，以确定其本身及其衍生物抑制黄嘌呤氧化酶的能力。

目的：该研究旨在利用天然成分以及抗氧化潜力开发新的黄嘌呤氧化酶抑制剂。

方法：在本报告中，我们设计并合成了与醇和胺杂交形成氨基酸酯键和酰胺键的丁香酸衍生物。评价合成化合物的抗氧化剂和黄嘌呤氧化酶抑制潜能。

结果：研究结果表明SY3产生非常好的黄嘌呤氧化酶抑制活性。所有化合物均显示出非常好的抗氧化活性。对丁香酸衍生物的酶动力学研究表明，它具有竞争性的潜在抑制XO能力的作用，IC50值为07.18μM-15.60μM，而SY3被认为是活性最高的衍生物。分子模拟显示，新的丁香酸衍生物与位于XO结合位点内的氨基酸残基SER1080，PHE798，GLN1194，ARG912，GLN 767，ALA1078和MET1038相互作用。抗氧化剂活性的结果表明，所有衍生物都显示出非常好的抗氧化剂潜力。

结论：分子对接被证明是设计新的丁香酸衍生物的有效和选择性工具。两种天然成分的这种杂交可产生理想的黄嘌呤氧化酶抑制剂，并具有改善的活性。