Optimization of chelating agent structure for the mobilization of aged renal and hepatic cadmium deposits: sodium N-benzyl-4-O-(.beta.-D-galactopyranosyl)-D-glucamine-N-carbodithioate

Publisher Website
Google Scholar
Abstract
An examination of the structure-activity relationships for the mobilization of intracellular cadmium by previously synthesized dithiocarbamates indicates that superior compounds can be prepared by increasing the molecular weight by using bulky polar but nonionic substituents. This suggested the synthesis and characterization of sodium N-benzyl-4-O-(.beta.-D-galactopyranosyl)-D-glucamine-N-carbodithioate. The preparation of this compound and its characterization as an agent for the mobilization of aged renal and hepatic cadmium deposits in mice show it to be superior to the compounds reported earlier which have been used for this purpose. Five ip injections of 0.40 mmol/kg reduced hepatic cadmium levels to 35% of their initial level and renal cadmium levels to 37%. The nature of the structural factors responsible for the efficacy of such agents is outlined as well as the relationship of these to the toxicity of the compounds and their cadmium complexes. These factors indicate clearly the differences in the molecular requirements for the mobilization of extracellular and intracellular toxic metal ions. The requirement that intracellular toxic metals be mobilized places several constraints on the structures of potentially efficacious compounds in addition to the thermodynamic and kinetic restrictions imposed by the requirements for extracellular efficacy.