The Formation of Sulfur Oxoacid Generators and the Effects of Dimedone on the Breakdown of Disulfiram

Cardiovascular disease (CVD) is the largest cause of death in the United States. Drugs that generate the small gaseous molecule Nitric Oxide (NO) have been used for hundreds of years to treat cardiovascular disease. Recently, Hydrogen Sulfide (H2S), another small gaseous molecule has been shown to have similar effects in the cardio vasculature; both NO and H2S affect the cGMP pathway by inhibiting PDE, a cardiovascular signaling molecule that decyclizes cGMP. Multiple drugs have been developed to release H2S in cells. The Farmer lab has identified small oxoacids of sulfur (SOS) as endogenously produced metabolites of H2S, which may play a role in its activity. The lab has also identified several families of compounds which release these metabolites, and these compounds show unusual activity in models of CVD. In this work, attempts were made to expand and improve the syntheses of these compounds, which include N,N'-(1,2,4,5-tetrathiane-3,6-diylidene)bis(N-ethylethanamine) dication (BITT2+) and diethyldithiocarbamate mono/di-oxide anions (DeDTCO1/2)-. Additional experiments were performed to assess if the SOS generation were important in the known activity of disulfiram and BITT2+ against melanoma in cell culture. Specifically, whether trapping SOS chemically inhibited generation of a toxic Cu(DeDTC)2 complex. Only initial experiments on the formation of the Cu(DeDTC)2 complex while trapping SOS could be completed.