Journal: Drug Design, Development and Therapy

Article Title: Novel Pyrazole-3-Cyano-2-Pyridinone Hybrids as Multitarget Anti-Inflammatory Agents: Synthesis, Computational Modeling, and Biological Evaluation

doi: 10.2147/DDDT.S570813

Figure Lengend Snippet: Binding conformations of the investigated most active pyrazole/3-cyanopyridinone candidate 5k ( A 3 ) related to celecoxib and etoricoxib references within the active site of the COX-2 enzyme. Two-dimensional schematic depicting key molecular interactions between celecoxib ( A 1 ), etoricoxib ( A 2 ), and 5k compound ( A 3 ) and the COX-2 active site. Three-dimensional representation illustrating the spatial orientations of compounds celecoxib ( B 1 ), etoricoxib ( B 2 ), and 5k ( B 3 ) (rendered in green cyan stick format) within the COX-2 binding pocket. Surface visualization of the COX-2 protein (depicted in brick red), demonstrating the surface-bound conformation of celecoxib ( C 1 ), etoricoxib ( C 2 ), and 5k ( C 3 ) compounds using a green cyan space-filling model.

Article Snippet: Molecular dynamics (MD) simulation analysis of compound 5k in comparison with the reference drugs celecoxib and, each bound to the COX-2 active site (celecoxib A 1 , etoricoxib A 2 , and compound 5k A 3 ).

Techniques: Binding Assay

Journal: Drug Design, Development and Therapy

Article Title: Novel Pyrazole-3-Cyano-2-Pyridinone Hybrids as Multitarget Anti-Inflammatory Agents: Synthesis, Computational Modeling, and Biological Evaluation

doi: 10.2147/DDDT.S570813

Figure Lengend Snippet: Molecular dynamics (MD) simulation analysis of compound 5k in comparison with the reference drugs celecoxib and, each bound to the COX-2 active site (celecoxib A 1 , etoricoxib A 2 , and compound 5k A 3 ). Root Mean Square Deviation (RMSD) plots for the COX-2 protein (gray) and the respective ligands (red), illustrating the structural stability of the complexes over the simulation period. (celecoxib B 1 , etoricoxib B 2 , and compound 5k B 3 ) Root Mean Square Fluctuation (RMSF) plots of COX-2 residues, highlighting regions of local flexibility influenced by ligand binding. (celecoxib C 1 , etoricoxib C 2 , and compound 5k C 3 ) Two-dimensional interaction maps depicting key ligand–protein interactions were consistently maintained throughout the simulation. (celecoxib D 1 , etoricoxib D 2 , and compound 5k D 3 ) Histograms showing the frequency and nature of ligand–protein interactions, offering insights into the stability and durability of binding over time.

Article Snippet: Molecular dynamics (MD) simulation analysis of compound 5k in comparison with the reference drugs celecoxib and, each bound to the COX-2 active site (celecoxib A 1 , etoricoxib A 2 , and compound 5k A 3 ).

Techniques: Comparison, Ligand Binding Assay, Binding Assay