Synthesis and biological evaluation of 5-nitropyrimidine-2,4-dione analogues as inhibitors of nitric oxide and iNOS activity.

ABSTRACT

Fifty two compounds based on 5-nitropyrimidine-2,4-dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50 8.6 µm) on lipopolysaccharide-induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50 6.2 µm), as well as exerted no potential cytotoxicity (IC50 > 80.0 µm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan-induced paw edema of male ICR mice.