Effect of imidazo[1,2-a]pyrimidine derivatives on leukocyte function

Objective and Design: A series of six imidazo [1,2-a]pyrimidine (IP) deriva tives were evaluated for their effects on leukocyte functions in vitro as w ell as on the inflammatory response induced by zymosan in the mouse air pou ch. Materials and Subjects: Human neutrophils and murine peritoneal macrophages were used for in vitro assays. Mouse air pouch was performed in Swiss mice . Treatment: Test compounds were incubated with either human neutrophils or m ouse peritoneal macrophages at concentrations not showing cytotoxic effects . For in vivo experiments, IPs were injected into the air pouch. Methods: Elastase and myeloperoxidase release, superoxide generation and LT B4 production were assayed in human neutrophils treated with different stim uli. Mouse peritoneal macrophages were stimulated with lipopolysaccharide ( LPS), followed by determination of nitrite and PGE, levels in supernatants. Zymosan was injected into six days-old mouse air pouches. Dunnett's t-test was employed for statistical analysis. Results: All IPs inhibited human neutrophil degranulation with IC50 values in the muM range. IP-1, IF-2 and IF-5 also decreased superoxide generation. In LPS-stimulated macrophages, IP-4 and IP-6 inhibited nitrite production with a moderate reduction in PGE, generation. In addition, these two compou nds at 100 nmol/pouch inhibited leukocyte migration and LTB4 levels in the exudate of the mouse air pouch. Conclusions: Imidazo [1,2 -a]pyrimidines are a class of compounds with anti inflammatory potential.