A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti-inflammatory Drugs

In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for theirin vitro anti-inflammatory activity. The effect of the selected molecules was confirmed in anin vivo inflammatory model. We also analyzed whether the effects were caused by inhibition of nuclear factor kappa B (NF- κB) transcription factor transmigration. Of the eight imidazoles tested, methyl 1-allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric oxide metabolites and pro-inflammatory cytokine (TNF- α, IL-6, and IL-1β) secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte migration and exudate formation in the pleural cavity of mice challenged with carrageenan. Furthermore, imidazole8 reverted the oxidative stress pattern triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase, superoxide dismutase, catalase, and glutathione S-transferase activities and reducing the production of nitric oxide metabolites and thiobarbituric acid-reactive substances. Finally, these effects can be attributed, at least in part, to the ability of this compound to prevent NF- κB transmigration. In this context, our results demonstrate that imidazole8 has promising potential as a prototype for the development of a new anti-inflammatory drug to treat inflammatory conditions in which NF- κB and oxidative stress play a prominent role.Graphical Abstractᅟ
Source: Inflammation - Category: Allergy & Immunology Source Type: research