NO-Donors, part 3: nitrooxyacylated thiosalicylates and salicylates - synthesis and biological activities

Organic nitrates release nitric oxide when incubated with thiosalicylic aci d. S-Nitrooxyacylated esters and amides of thiosalicylic acid, together wit h the corresponding salicylates, were synthesized in order to perform a fir st in vitro evaluation of these new nitrate-thiol-hybrid prodrugs. These pr odrugs might release NO in vivo after biotransformation without the use of endogenous reductives. None of these prodrugs released NO spontaneously whe n dissolved in buffer solution, but they did activate soluble guanylyl cycl ase and induced vasodilatation of phenylephrine-pretreated male Wistar rat aorta in a potency range between that of isosorbiddinitrate and glycerole t rinitrate. (C) 1999 Editions scientifiques et medicales Elsevier SAS.