Department of Pharmaceutical Sciences, M.D. University Rohtak, Rohtak, Haryana, India.
Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D. University, Rohtak, Haryana, India.
Med Chem. 2020;16(5):643-653. doi: 10.2174/1573406415666191004134346.
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.
The study aimed to develop new xanthine oxidase inhibitors from natural constituents along with the antioxidant potential.
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 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.
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.
黄嘌呤氧化酶（XO；EC 1.17.3.2）被认为是治疗和管理由于血液中尿酸水平升高而导致的病理状况的有效药物靶点。黄嘌呤氧化酶在催化氧化羟化次黄嘌呤生成黄嘌呤以及进一步催化黄嘌呤生成尿酸方面发挥着重要作用，因此它在高尿酸血症和痛风的产生中发挥着重要作用。在这项研究中，我们探索了丁香酸，一种生物活性酚酸，以确定其本身及其衍生物抑制黄嘌呤氧化酶的能力。
本研究旨在从天然成分中开发新的黄嘌呤氧化酶抑制剂，并具有抗氧化潜力。
在本报告中，我们设计并合成了与醇和胺杂交的丁香酸衍生物，通过分子对接形成酯和酰胺键。评估了合成化合物的抗氧化和黄嘌呤氧化酶抑制潜力。
研究结果表明，SY3 产生了非常好的黄嘌呤氧化酶抑制活性。所有化合物均表现出非常好的抗氧化活性。对丁香酸衍生物进行的酶动力学研究表明，它们以竞争性方式对 XO 能力具有潜在的抑制作用，IC50 值范围为 07.18μM-15.60μM，SY3 是最活跃的衍生物。分子模拟表明，新的丁香酸衍生物与 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。抗氧化活性结果表明，所有衍生物均表现出非常好的抗氧化潜力。
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。这两种天然成分的杂交可能会产生具有改善活性的理想黄嘌呤氧化酶抑制剂。
