Novel inhibitors of nitric oxide synthase with antioxidant properties

We previously described a series of imidazole-based inhibitors substituted at N-1 with an arylethanone chain as interesting inhibitors of neuronal nitric oxide synthase (nNOS), endowed with good selectivity vs endothelial nitric oxide synthase (eNOS). As a follow up of these studies, several analogs characterized by the presence of substituted imidazoles or other mono or bicyclic nitrogen-containing heterocycles instead of simple imidazole were synthesized, and their biological evaluation as in vitro inhibitors of both nNOS and eNOS is described herein. Most of these compounds showed improved nNOS and eNOS inhibitory activity with respect to reference inhibitors. Selected compounds were also tested to analyze their antioxidant properties. Some of them displayed good capacity to scavenge free radicals and ability to reduce lipid peroxidation.

Graphical abstractA series of new mono or bicyclic nitrogen-containing heterocycles linked to an arylethanone chain were prepared and evaluated for their inhibitory potency vs nNOS and eNOS. Selected compounds were also tested to assay their antioxidant properties.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New mono or bicyclic nitrogen-containing heterocycles linked to an arylethanone chain were synthesized. ► Inhibitory potency vs nNOS and eNOS in the low micromolar range was obtained. ► Selected compounds were tested to assay their antioxidant properties. ► Some compounds emerged for the combination of nNOS inhibition and antioxidant activity in the same molecule.