title: New nitric oxide or hydrogen sulfide releasing aspirins.
abstract: A new series of (((R-oxy)carbonyl)oxy)methyl esters of aspirin (ASA), bearing nitric oxide (NO) or hydrogen sulfide (H(2)S) releasing groups, was synthesized, and the compounds were evaluated as new ASA co-drugs. All the products were quite stable in buffered solution at pH 1 and 7.4. Conversely, they were all rapidly metabolized, producing ASA and the NO/H(2)S releasing moiety used for their preparation. Consequent on ASA release, the compounds were capable of inhibiting collagen-induced platelet aggregation of human platelet-rich plasma (PRP). The simple NO/H(2)S donor substructures were able to relax contracted rat aorta strips, with a NO- and H(2)S-dependent mechanism, respectively, but they either did not trigger antiaggregatory activity or displayed antiplatelet potency markedly below that of the related co-drug. The new products might provide a safer and improved alternative to the use of ASA principally in its anti-inflammatory and antithrombotic applications.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Torino, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Lazzarato
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chegaev
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marini
authors.forename: Barbara
authors.initials: B
authors.lastname: Rolando
authors.forename: Emily
authors.initials: E
authors.lastname: Borretto
authors.forename: Stefano
authors.initials: S
authors.lastname: Guglielmo
authors.forename: Sony
authors.initials: S
authors.lastname: Joseph
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Stilo
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D001013:Aorta, Thoracic / Q000187:drug effects; D001241:Aspirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001241:Aspirin; D006862:Hydrogen Sulfide