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 100 mu M, 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.

Searching for new NO-donor aspirin-like molecules: furoxanylacyl derivatives of salicylic acid and related furazans

LAZZARATO, Loretta;CENA, Clara;ROLANDO, Barbara;MARINI, Elisabetta;LOLLI, Marco Lucio;GUGLIELMO, Stefano;FRUTTERO, Roberta;GASCO, Alberto
2011

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 100 mu M, 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.
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5852
5860
NO-aspirins; NO-NSAIDs; multitarget drugs; anti-inflammatory activity
Lazzarato Loretta; Cena Clara; Barbara Rolando; Elisabetta Marini; Marco Lucio Lolli; Guglielmo Stefano; Elena Guaita; Giuseppina Morini; Gabriella Coruzzi; Roberta Fruttero; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/131731
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