Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor

P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production proteins (iNOS, NF-kB, COX-2). In this study, drug repurposing strategies were followed to repositioning a series B-RAF V600E imidazol-5-yl pyridine inhibitors inhibit P38α kinase. A group 25 reported kinase used build pharmacophore model for mapping target compounds proving their affinity binding active site. Target evaluated potency against kinase, 11a 11d most potent (IC50 = 47 nM 45 nM, respectively). addition, compound effectively inhibited proinflammatory TNF-α, 1L-6, 1L-1β LPS-induced RAW 264.7 macrophages with IC50 values 78.03 17.6 µM 82.15 respectively. The tested anti-inflammatory activity by detecting reduction Nitric oxide (NO) prostaglandin (PGE2) LPS-stimulated macrophages. Compound exhibited satisfied inhibitory PGE2 NO 0.29 0.61 µM, Molecular dynamics simulations inhibitor carried out illustrate its conformational stability site