Searching for new NO-donor aspirin-like molecules: a new class of nitrooxy-acyl derivatives of salicylic acid.
A new class of products in which the phenol group of salicylic acid is linked to alkanoyl moieties bearing nitrooxy functions has been synthesized and studied for their polyvalent actions. The products were stable in acid and neutral media, while they were hydrolyzed in human serum. Their half-lives were dependent upon the structure of alkanoyl moieties. The products showed anti-inflammatory activities similar to aspirin when tested in the carrageenan-induced paw edema assay in the rat. Interestingly, unlike aspirin, they showed reduced or no gastrotoxicity in a lesion model in rats at equimolar doses. A number of them were able to inhibit platelet aggregation induced by collagen in human platelet-rich plasma. All of the products were capable of relaxing rat aortic strips precontracted with phenylephrine in a concentration-dependent manner. Selected members of this new class of nonsteroidal anti-inflammatory drugs might represent possible safer alternatives to aspirin in different clinical settings.
Lazzarato
Loretta
L
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, Turin, Italy.
Donnola
Monica
M
Rolando
Barbara
B
Marini
Elisabetta
E
Cena
Clara
C
Coruzzi
Gabriella
G
Guaita
Elena
E
Morini
Giuseppina
G
Fruttero
Roberta
R
Gasco
Alberto
A
Biondi
Stefano
S
Ongini
Ennio
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D002351:Carrageenan; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D006868:Hydrolysis; D008297:Male; D015394:Molecular Structure; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D009574:Nitro Compounds / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D010975:Platelet Aggregation Inhibitors; D012996:Solutions; D014665:Vasodilator Agents; D014867:Water; D002351:Carrageenan; D020156:Salicylic Acid; D001241:Aspirin