Antiinflammatory, gastrosparing, and antiplatelet properties of new NO-donor esters of aspirin.
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.
Cena
Clara
C
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
Lolli
Marco L
ML
Lazzarato
Loretta
L
Guaita
Elena
E
Morini
Giuseppina
G
Coruzzi
Gabriella
G
McElroy
Stuart P
SP
Megson
Ian L
IL
Fruttero
Roberta
R
Gasco
Alberto
A
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D001241:Aspirin