NO-glibenclamide derivatives: prototypes of a new class of nitric oxide-releasing anti-diabetic drugs.

Endothelial dysfunction and consequent reduction of biosynthesis of endogenous nitric oxide (NO) play an important pathogenetic role in the cardiovascular complications associated with type II diabetes. In this work, the hybrid drugs 3a and 3b, nitrooxymethylbenzoate-derivatives of 1 (which is a hydroxylated active metabolite of glibenclamide 2), are reported. The pharmacodynamic characterization of 3b showed that its hypoglycaemic activity is enriched with additional NO-donor effects, conferring vasorelaxing and anti-platelet properties of potentially great usefulness for diabetes-related cardiovascular disorders.