title: Antiinflammatory, gastrosparing, and antiplatelet properties of new NO-donor esters of aspirin.
abstract: A new series of NSAIDs in which aspirin is joined by an ester linkage to furoxan moieties, with different ability to release NO, were synthesized and tested for NO-releasing, antiinflammatory, antiaggregatory, and ulcerogenic properties. Related furazan derivatives, aspirin, its propyl ester, and its gamma-nitrooxypropyl ester were taken as references. All the products described present an antiinflammatory trend, maximized in derivatives 12, 16, and 17, they are devoid of acute gastrotoxicity, principally due to their ester nature, and show an antiplatelet activity primarily determined by their ability to release NO. They do not behave as aspirin prodrugs in human serum.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Cena
authors.forename: Marco L
authors.initials: ML
authors.lastname: Lolli
authors.forename: Loretta
authors.initials: L
authors.lastname: Lazzarato
authors.forename: Elena
authors.initials: E
authors.lastname: Guaita
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Morini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Coruzzi
authors.forename: Stuart P
authors.initials: SP
authors.lastname: McElroy
authors.forename: Ian L
authors.initials: IL
authors.lastname: Megson
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001241:Aspirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004487:Edema / Q000188:drug therapy; D004952:Esters; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009336:Necrosis; D009569:Nitric Oxide / Q000097:blood; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010437:Peptic Ulcer / Q000139:chemically induced / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D001241:Aspirin