Computational Analysis and Synthesis of Syringic Acid Derivatives as Xanthine Oxidase Inhibitors.
Syringic acid
antioxidant
hyperuricemia
molecular docking
uric acid
xanthine oxidase
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2020
2020
Historique:
received:
12
03
2019
revised:
07
05
2019
accepted:
23
08
2019
pubmed:
5
10
2019
medline:
2
4
2021
entrez:
5
10
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
The study aimed to develop new xanthine oxidase inhibitors from natural constituents along with the antioxidant potential.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31584375
pii: MC-EPUB-101195
doi: 10.2174/1573406415666191004134346
doi:
Substances chimiques
Enzyme Inhibitors
0
Gallic Acid
632XD903SP
syringic acid
E390O181H5
Xanthine Oxidase
EC 1.17.3.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
643-653Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.