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 NOinduced 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.

(Nitrooxyacyloxy)methyl esters of aspirin as novel nitric oxide releasing aspirins

LAZZARATO, Loretta;ROLANDO, Barbara;CHEGAEV, Konstantin;MARINI, Elisabetta;CENA, Clara;DI STILO, Antonella;FRUTTERO, Roberta;GASCO, Alberto
2009

Abstract

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 NOinduced 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.
JOURNAL OF MEDICINAL CHEMISTRY
52
5058
5068
http://pubs.acs.org/doi/abs/10.1021/jm900587h
organic nitrates; NO-aspirins; NO-NSAIDs; multitarget drugs
Loretta Lazzarato; Monica Donnola; Barbara Rolando; Konstantin Chegaev; Elisabetta Marini; Clara Cena; Antonella Di Stilo; Roberta Fruttero; Stefano Biondi; Ennio Ongini; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/64090
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