Synthesis and anti-inflammatory structure–activity relationships of thiazine–quinoline–quinones: Inhibitors of the neutrophil respiratory burst in a model of acute gouty arthritis

Sixteen new thiazine–quinoline–quinones have been synthesised, plus one bicyclic analogue. These compounds inhibited neutrophil superoxide production in vitro with IC50s as low 60 nM. Compounds with high in vitro anti-inflammatory activity were also tested in a mouse model of acute inflammation. The most active compounds inhibited both neutrophil infiltration and superoxide production at doses 2.5 μmol/kg, highlighting their potential for development as novel NSAIDs.

Synthesised thiazine–quinoline–quinones were assayed for inhibition of superoxide production in vitro. Analogues were tested in vivo for inhibition of neutrophil superoxide production and infiltration induced by monosodium urate crystals.Figure optionsDownload as PowerPoint slide