title: Searching for new NO-donor aspirin-like molecules: Furoxanylacyl derivatives of salicylic acid and related furazans.
abstract: A new group of derivatives of salicylic acid containing NO-donor furoxans, and the related des-NO-furazans, were synthesized and evaluated as new aspirin-like molecules. Their stability was assessed in acid (pH 1) and physiological solutions (pH 7.4), and in human serum. No compound exhibited COX-inhibitory activity against COX-1 and COX-2 isoforms, when tested up to 100μM, respectively, on isolated platelets and on monocytes. Phenylsulfonyl- and cyano-substituted furoxans inhibited platelet aggregation induced by collagen in human platelet-rich plasma, through a cGMP dependent mechanism. Furoxan derivatives displayed cGMP-dependent vasodilator activities, tested on rat aorta strips precontracted with phenylephrine. All products showed anti-inflammatory activity similar to that of ASA, tested on rats by the carrageenan-induced paw edema assay. Unlike ASA, all products showed markedly reduced gastrotoxicity in a rat lesion model.
authors: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
authors: Loretta
authors: L
authors: Lazzarato
authors: Clara
authors: C
authors: Cena
authors: Barbara
authors: B
authors: Rolando
authors: Elisabetta
authors: E
authors: Marini
authors: Marco Lucio
authors: ML
authors: Lolli
authors: Stefano
authors: S
authors: Guglielmo
authors: Elena
authors: E
authors: Guaita
authors: Giuseppina
authors: G
authors: Morini
authors: Gabriella
authors: G
authors: Coruzzi
authors: Roberta
authors: R
authors: Fruttero
authors: Alberto
authors: A
authors: Gasco
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001241:Aspirin / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D020156:Salicylic Acid / Q000737:chemistry*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C010166:furoxans; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D020156:Salicylic Acid; D001241:Aspirin