title: NO-glibenclamide derivatives: prototypes of a new class of nitric oxide-releasing anti-diabetic drugs.
abstract: 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.
authors: Dipartimento di Psichiatria, Neurobiologia, Farmacologia, Biotecnologie, Università di Pisa, Via Bonanno, 6, I-56126 Pisa, Italy. calderone@farm.unipi.it
authors: Vincenzo
authors: V
authors: Calderone
authors: Simona
authors: S
authors: Rapposelli
authors: Alma
authors: A
authors: Martelli
authors: Maria
authors: M
authors: Digiacomo
authors: Lara
authors: L
authors: Testai
authors: Scilla
authors: S
authors: Torri
authors: Piero
authors: P
authors: Marchetti
authors: Maria C
authors: MC
authors: Breschi
authors: Aldo
authors: A
authors: Balsamo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy*; D005905:Glyburide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005905:Glyburide