Docking Study, Synthesis, and Anti-Inflammatory Potential of Some New Pyridopyrimidine-Derived Compounds.
J Inflamm Res
; 15: 451-463, 2022.
Article
en En
| MEDLINE
| ID: mdl-35125880
ABSTRACT
BACKGROUND AND PURPOSE:
Because of gastrointestinal irritation and kidney toxicity associated with non-steroidal anti-inflammatory drugs and the cardiovascular problems of Coxibs use, developing novel anti-inflammatory agents with reduced toxicity and improved selectivity remains a major challenge. Depending on our previous work, a novel series of pyridopyrimidinones IIIa-i has been synthesized via reaction of 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (I) and phenyldiazenyl aromatic aldehydes (IIa-i). All the new constructed compounds were fully characterized by elemental and spectral analysis.METHODS:
The target compounds IIIa-i were investigated for their potential towards COX inhibition, anti-inflammatory properties using carrageenan induced edema model in rat paw, and the ulcer indices of the most active members.RESULTS:
The ethyl pyridopyrmidinone-benzoates IIIf, IIIg and IIIh showed superior inhibitory activity of carrageenan induced edema to celecoxib. Furthermore, the pyridopyrimidinones IIId, IIIf, IIIg, and IIIi exerted improved COX-2 inhibitory activity (IC50 = 0.67-1.02 µM) comparing to celecoxib (IC50 = 1.11 µM). Moreover, the gastric ulcerogenic potential assay of compounds IIIf-h revealed their lower ulcerogenic liability than indomethacin with comparable effect to celecoxib.CONCLUSION:
Virtual docking investigation of the most active candidates IIId, IIIf, IIIg and IIIi in the active site of COX-2 enzyme showed that these compounds implied interaction and binding motif similar to the cocrystallized ligand bromocelecoxib.
Texto completo:
1
Banco de datos:
MEDLINE
Idioma:
En
Año:
2022
Tipo del documento:
Article