Docking Study, Synthesis, and Anti-Inflammatory Potential of Some New Pyridopyrimidine-Derived Compounds

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-1 H -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 (IC 50 = 0.67–1.02 µM) comparing to celecoxib (IC 50 = 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.

Exploring the Binding Affinity and Molecular Interactions: A Comprehensive Study on the Molecular Docking of Benzimidazole Derivatives

“…3D crystallographic structure of COX receptor 20 (PDB ID-1CX2, 5GMN, 7OCS), LOX receptor (2E77, 3FG1, 1YXJ), Estrogen receptor (4MOE, 2IOG, 5AAU, 2POG, 1XPC, 2QXS) were retrieved from Protein Data Bank 21 and used as protein target for our in-silico studies which is shown in Figure 2. In the process facilitated by Discovery Studio Visualizer, any bound water, hetero atoms, and undesired side chains were eliminated from the protein molecule.…”

Antioxidant and Antimicrobial Potential of 1,8‐Naphthyridine Based Scaffolds: Design, Synthesis and in Silico Simulation Studies within Topoisomerase II

“…The search of convenient synthetic approaches for the construction of new compounds with potential biological and pharmacological effects is an extension of our efforts to find convenient synthetic approaches [48–60] . In connection with these aforesaid observations, the purpose of this study is to develop novel bioactive isolated spiro β ‐Lactam and thiazolidinone derivatives bearing 1,8‐naphthyridine moiety.…”

Design, Synthesis, Docking Study of Pyrazolohydrazinopyrimidin‐4‐one Derivatives and Their Application as Antimicrobials

“…These drugs act through suppressing dihydropteroate synthase DHPS enzyme [42,43] . In the light of medicinal attributes of pyrazole and pyrimidine heterocycles and our work related to the discovery of bioactive candidates, [44–56] we introduce herein the design, construction and antimicrobial screening of novel pyrazole‐pyrimidine hybrids utilizing fragment‐based drug design approach. Our scope in this study was to construct novel pyrazole‐pyrimidine derivatives via the merge between pyrimidine core and pyrazole nucleus which are important scaffolds as antimicrobial agents with dihydropteroate synthase inhibitory effect.…”