Computational Analysis and Synthesis of Syringic Acid Derivatives as Xanthine Oxidase Inhibitors

Author(s): Neelam Malik, Anurag Khatkar*, Priyanka Dhiman

Journal Name: Medicinal Chemistry

Volume 16 , Issue 5 , 2020


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Abstract:

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.

Keywords: Syringic acid, xanthine oxidase, molecular docking, antioxidant, hyperuricemia, uric acid.

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VOLUME: 16
ISSUE: 5
Year: 2020
Published on: 07 August, 2020
Page: [643 - 653]
Pages: 11
DOI: 10.2174/1573406415666191004134346
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