title: (Nitrooxyacyloxy)methyl esters of aspirin as novel nitric oxide releasing aspirins.
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 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.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Universita degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Lazzarato
authors.forename: Monica
authors.initials: M
authors.lastname: Donnola
authors.forename: Barbara
authors.initials: B
authors.lastname: Rolando
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chegaev
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marini
authors.forename: Clara
authors.initials: C
authors.lastname: Cena
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Stilo
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.forename: Stefano
authors.initials: S
authors.lastname: Biondi
authors.forename: Ennio
authors.initials: E
authors.lastname: Ongini
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
mesh_terms: 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
chemical_list: D004952:Esters; D009566:Nitrates; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D001241:Aspirin