Design and Synthesis of Novel 1-hydroxy-2,4,5-triaryl Imidazole Derivatives as Anti-cytokine Agents

Among recent advances in the identification of anti-inflammation agents, anti-cytokines(like interleukin-1), related to p38 mapk families play an important role; here in we designednew effective and low toxic anti-cytokine agents based on 1-hydroxy-2,4,5-triaryl imidazolederivatives. the reaction of oximoinoketone intermediate with ten different aromatic aldehydeand ammonium acetate in refluxing acetic acid condition give imidazole derived product, theil-1β inhibitory assay were performed on human pbmcs (peripheral blood mononuclear cells)using an enzyme-linked immunosorbent assay (elisa) kit and then in computational part thebinding mode of the best compound was accomplished by docking in crystal structure of p38map kinase (pdb id: 1a9u) compared with sb202190 as standard drug. all compounds weresynthesized and evaluated in biological assay showing the inhibitory activity from 28% to 82%compared to sb202190 and binding mode analysis revealed that the hydrogen-bond interactionswith residues (met109, val30) were key point in inhibitor binding. compound 5g clearly provedthe best inhibitory action and could be further utilized for designing newer anti-cytokine agentsand p38α map kinase potentially inhibitory action.