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The Furoxan System: Design of Selective Nitric Oxide (NO) Donor Inhibitors of COX‐2 Endowed with Anti‐Aggregatory and Vasodilating Activities
Author(s) -
Del Grosso Erika,
Boschi Donatella,
Lazzarato Loretta,
Cena Clara,
Di Stilo Antonella,
Fruttero Roberta,
Moro Stefano,
Gasco Alberto
Publication year - 2005
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200590065
Subject(s) - furoxan , chemistry , nitric oxide , vasodilation , in vitro , pharmacology , stereochemistry , combinatorial chemistry , biochemistry , organic chemistry , medicine , cardiology
Several NO donor 3,4‐diphenylfuroxan (=3,4‐diphenyl‐1,2,5‐oxadiazole 2‐oxide) derivatives were synthesized and tested for their COX‐inhibiting activities. The products were found to be selective COX‐2 inhibitors, similar to the structurally related furazans (3,4‐diphenyl‐1,2,5‐oxadiazole), devoid of the NO release property. This behavior was confirmed by a molecular‐docking study. The NO‐dependent platelet anti‐aggregatory and vasodilating activities of the new furoxans 5 – 7 were studied in vitro. These properties can be modulated by inserting an appropriate spacer between the 4‐phenyl group and the furoxan ring, giving rise to new, selective COX‐2 furoxan derivatives endowed with anti‐aggregatory and vasodilating activities, and with potentially reduced cardiotoxicities.