Anti‐inflammatory effects of synthetic compound KT‐14480 in lipopolysaccharide‐stimulated microglia cells

Objectives Neurodegenerative diseases have a prominent inflammatory component. Several synthetic fluorovinyloxyacetamide derivatives were screened by microglia cell‐based assay in order to identify novel compounds that inhibit the inflammatory activation of microglia. Methods Microglia cell‐based nitric oxide assay was employed to screen the compounds. RT‐PCR and ELISA were conducted to evaluate the expression of inflammatory gene expression. Molecular mechanisms were determined by western blot analysis, immunocytochemistry, EMSA, and microglia/neuroblastoma cocultures. Key findings A fluorovinyloxyacetamide compound KT‐14480 significantly suppressed nitric oxide production in lipopolysaccharide‐stimulated microglia cells. KT‐14480 also suppressed the secretion and expression of several inflammatory mediators such as tumour necrosis factor‐α, interleukin‐1β and inducible nitric oxide synthase. Additional studies showed that these inhibitory effects were accompanied by the suppression of nuclear factor‐κB and neuroprotection in the microglia/neuroblastoma coculture. Conclusions Our results indicate that the anti‐inflammatory compound KT‐14480 may be a novel therapeutic drug candidate against neuroinflammatory diseases.