Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H2S) donors for lowering blood pressure

Abstract Hydrogen sulfide (H 2 S) is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H 2 S supply, we report here the preparation and the H 2 S release kinetics from a series of structurally diversified thioamides, thiolactams and thioureas. Three different thionation methods based on the usage of a phosphorus pentasulfide and Lawesson reagent were applied to prepare the target thioamides and thiolactams. Furthermore, obtained H 2 S donors were evaluated both in in vivo and in vitro studies. The kinetic parameters of the liberating H 2 S was determined and compared with NaHS and GYY4137 using two different detection technics i.e.; fluorescence labeling 7-azido-4-methyl-2 H -chromen-2-one and 5,5‘-dithiobis (2-nitrobenzoic acid), sulfhydryl probe, also known as the Ellman’s reagent. We have proved that the amount of releasing H 2 S from these compounds is controllable through structural modifications. Finally, the present study shows a hypotensive response to an intravenous administration of the developed donors in the anesthetized rats.