The furoxan system: design of selective nitric oxide (NO) donor inhibitors of COX-2 endowed with anti-aggregatory and vasodilating activities.
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.
Del Grosso
Erika
E
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università degli Studi del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy.
Boschi
Donatella
D
Lazzarato
Loretta
L
Cena
Clara
C
Di Stilo
Antonella
A
Fruttero
Roberta
R
Moro
Stefano
S
Gasco
Alberto
A
D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; D014665:Vasodilator Agents; C010166:furoxans; C116926:rofecoxib; D000068579:Celecoxib