Identification of potent and selective inhibitors of inducible or neuronal nitric oxide synthase (NOS) is of great interest because of their therapeutic potential for treatment of diseases mediated by overproduction of nitric oxide. Imidazole derivatives are described in the literature as inhibitors of various isoforms of NOS as well as inhibitors of various oxidoreductase enzymes. In this paper, we describe the synthesis and inhibitory activities towards neuronal rat recombinant NOS (nNOS), inducible mouse macrophage NOS (iNOS) and endothelial human platelet NOS (eNOS) of a series of 1-substituted imidazoles i.e. N-phenacyl, N-phenethyl- and N-phenyl-hydroxyethyl-imidazoles. The results show that the N-(4-nitrophenacyl)imidazole 2e may be an interesting molecule. In fact, this substance, although active only in the micromolar range on nNOS, could be considered for ist selectivity for nNOS versus eNOS, in particular if compared with the reference substances (imidazole, 1-phenyl-imidazole and nitro-arginine). Thus 2e represents a chemical structure which can be easily modified in order to improve the observed potency and selectivity.

N-substituted-imidazoles as inhibitors of nitric oxide synthase: a preliminary screening

SALERNO, Loredana;SIRACUSA, Maria Angela;DI GIACOMO, Claudia;
1999

Abstract

Identification of potent and selective inhibitors of inducible or neuronal nitric oxide synthase (NOS) is of great interest because of their therapeutic potential for treatment of diseases mediated by overproduction of nitric oxide. Imidazole derivatives are described in the literature as inhibitors of various isoforms of NOS as well as inhibitors of various oxidoreductase enzymes. In this paper, we describe the synthesis and inhibitory activities towards neuronal rat recombinant NOS (nNOS), inducible mouse macrophage NOS (iNOS) and endothelial human platelet NOS (eNOS) of a series of 1-substituted imidazoles i.e. N-phenacyl, N-phenethyl- and N-phenyl-hydroxyethyl-imidazoles. The results show that the N-(4-nitrophenacyl)imidazole 2e may be an interesting molecule. In fact, this substance, although active only in the micromolar range on nNOS, could be considered for ist selectivity for nNOS versus eNOS, in particular if compared with the reference substances (imidazole, 1-phenyl-imidazole and nitro-arginine). Thus 2e represents a chemical structure which can be easily modified in order to improve the observed potency and selectivity.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/41736
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