Water Soluble Furoxan Derivatives as NO Prodrugs

The synthesis, characterization, NO donor properties, and in vitro vasodilating activity of a series of water soluble furoxans (5−14a,b) are described. All of the compounds released NO when treated with a large excess of cysteine under physiological conditions (pH 7.4; 37 °C). The amount of NO produced after 1 h of incubation was evaluated by detecting nitrites, via the Griess reaction. Derivatives 5b, 7b, and 14b were able to release nitric oxide also in the absence of the thiol cofactor. The initial rates of NO release were determined at different concentrations, using a spectrophotometric technique based on the NO-induced oxidation of oxyhemoglobin (HbO2) to methemoglobin (MetHb). The initial rates of NO release were linearly dependent on the concentrations of the single compounds. The vasodilating potency (EC50) of all the derivatives was assessed on rat aortic strips precontracted with noradrenaline. Correlation between potency and initial NO release rate is discussed.