Evaluation of benzoylacetonitriles as novel anti-neuroinflammatory agents

AbstractInflammation in the central nervous system is associated with numerous neurological disorders, including multiple sclerosis, Parkinson ’s disease, Alzheimer’s disease, and ischemic stroke. Enhanced inflammatory events either drive these disorders directly or are consequences of disease processes. As such, the identification of novel classes of anti-neuroinflammatory agents may help address current treatment shortcomings. In thi s report, we describe the immunomodulatory activity of a series of benzoylacetonitriles in both BV2 and primary microglial cells. Molecules were evaluated for ability to suppress LPS-induced protein levels of IL-6. Analysis of these data afforded a clear structure-activity trend and identified7a as the most potent analog.7a suppressed numerous LPS-induced inflammatory mediators in a dose-dependent fashion in both cell types. Furthermore,7a suppressed activation of the NF κB pathway, suggesting a potential mechanism of action. Taken together, these studies demonstrate benzoylacetonitriles have broad anti-neuroinflammatory properties and should be further explored as potential treatments for relevant diseases.Graphical Abstract

Source: Medicinal Chemistry Research - March 23, 2023 Category: Chemistry Source Type: research