Potentiation of activation of soluble guanylate cyclase by YC-1, NO-donors and increase of the synergistic effect of YC-1 on NO-dependent activation of the enzyme by 1,2,3-triazolyl-1,2,5-oxadiazole derivatives

Abstract

The influence of (1H-1,2,3-triazol-1-yl)-1,2,5-oxadiazole derivatives: 4-amino-3-(5-methyl-4- ethoxycarbonyl-(1H-1,2,3-triazol-1-yl)-1,2,5-oxadiazole (TF4CH3) and 4,4'-bis(5-methel-4-ethoxycarbonyl-1H- 1,2,3-triazol-1-yl)-3,3'-azo-1,2,5-oxadiazole (2TF4CH3) on stimulation of human platelet soluble guanylate cyclase by YC-1, NO-donors (sodium nitroprusside, SNP, and spermine NONO) and on a synergistic increase of NO-dependent enzyme activation in the presence of YC-1 has been investigated. Both compounds increased guanylate cyclase activation by YC-1, potentiated guanylate cyclase stimulation by NO-donors and increased the synergistic effect of YC-1 on NO-dependent activation of soluble guanylate cyclase. The similarity in the properties of the examined TF4CH3 and 2TF4CH3 with that of YC-1 and the possible mechanism underlying the revealed properties of compounds used are discussed.