Chemical and Biological Proterties of Trivalent Methylarsenic Compounds, Monomethylarsonous Cysteine and Dimethylarsinous Cysteine

抄録

Although methylation of inorganic arsenicals has long been considered as a detoxification process, recent studies have indicated the synthesis of highly cytotoxic trivalent methylarsenicals during this process. Trivalent methylarsenicals may be generated as arsenical-glutathione conjugates such as dimethylarsinous glutathione (DMAs^IIIG), which may be formed as an intermediate during the methylation of inorganic arsenicals. Recently, we established the synthesis of DMAs^IIIG in our laboratory using a high performance thin-layer chromatography (HPTLC) plate. However, DMAs^IIIG is unstable under aqueous conditions and dissociates readily into dimethylarsinic acid (DMAs^V) and glutathione (GSH). Therefore, to overcome this obstacle, we employed cysteine as a thiol donor and synthesized monomethylarsonous cysteine (MMAs^IIIC) and dimethylarsinous cysteine (DMAs^IIIC). In this study, we used cysteine instead of GSH as the thiol donor and observed the in vitro cytolethality of synthetic MMAs^IIIC and DMAs^IIIC.