(Nitrooxyacyloxy)methyl esters of aspirin as novel nitric oxide releasing aspirins.
A series of (nitrooxyacyloxy)methyl esters of aspirin were synthesized and evaluated as new NO-donor aspirins. Different amounts of aspirin were released in serum from these products according to the nature of nitrooxyacyloxy moiety present. In the aromatic series, there is a rather good linear correlation between the amount of aspirin released and the potencies of the products in inhibiting platelet aggregation induced by collagen. Both the native compounds and the related nitrooxy-substituted acid metabolites were able to relax rat aorta strips precontracted with phenylephrine, in keeping with a NO-induced activation of the sGC as a mechanism that underlies the vasodilator effect. The products here described are new improved examples of NO-donor aspirins containing nitrooxy groups. They could represent an alternative to the use of aspirin in a variety of clinical applications.
Lazzarato
Loretta
L
Dipartimento di Scienza e Tecnologia del Farmaco, Universita degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
Donnola
Monica
M
Rolando
Barbara
B
Chegaev
Konstantin
K
Marini
Elisabetta
E
Cena
Clara
C
Di Stilo
Antonella
A
Fruttero
Roberta
R
Biondi
Stefano
S
Ongini
Ennio
E
Gasco
Alberto
A
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001241:Aspirin / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D004355:Drug Stability; D004952:Esters; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009566:Nitrates / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology
D004952:Esters; D009566:Nitrates; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D001241:Aspirin