Improved synthesis and anti-inflammatory activity of new fluorinated dihydropyranonaphthoquinone compounds.

This study presents the synthesis of new fluorinated dihydropyranonapthoquinone compounds by means of microwave-prompted four-component reactions using lawson, fluorinated aromatic aldehydes, ethyl 4,4,4-trifluoroacetoacetate and ammonium acetate. The products were thoroughly characterized by spectroscopic methods and assessed for their anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 macrophage cells. All synthesized compounds demonstrated notable inhibitory effects on NO production with IC50 ranging from 1.67 ± 0.02 to 28.81 ± 2.44 μM without causing significant toxicity. Interestingly, compound 8n showed the most potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 value of 1.67 ± 0.02 μM. Moreover, compounds 8c,h,i,l significantly decreased the levels of pro-inflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 macrophages. These results indicate the potential of these compounds as promising candidates for the development of new anti-inflammatory agents.