Amphipathic dithiocarbamates as cadmium antagonists: N-cyclohexyl-N-sulfonatoalkyl derivatives
Gale, G.R.; Atkins, L.M.; Smith, A.B.; Jones, S.G.; Jones, M.M.
Research Communications in Chemical Pathology and Pharmacology 58(3): 371-391
1987
ISSN/ISBN: 0034-5164 PMID: 3438572 Document Number: 288625
Disodium salts of the substituted dithiocarbamates (DTCs) N-cyclohexyl-N-(2-sulfonatoethyl) DTC, N-cyclohexyl-N-(3-sulfonatopropyl) DTC, and N-cyclohexyl-N-(2-hydroxy-3-sulfonatopropyl) DTC were synthesized and assessed as complexing agents for reducing organ concentrations of cadmium (Cd) in mice. At least one week after mice were given 0.03 mg of CdCl2.2.5 H2O containing 1.0 microCi of 109CdCl2 ip they were treated ip with various doses of each DTC. Administration of 4.44 mmoles/kg of each analog q2dx4 produced about a 60% reduction in the whole-body Cd burdens. There was approximately a 50% reduction of renal Cd concentrations and a greater than 90% reduction of hepatic Cd. There was no significant effect on the Cd levels in pancreas, spleen, testes, or brain. Mobilization of organ Cd stores led to excretion of Cd principally in the feces; treatment with 2.22 mmoles/kg of each analog qdx3 promoted a cumulative excretion of 32-40% of the administered metal. Rational design of potential Cd complexing agents is discussed with reference to the relative aqueous and lipid solubilities of the N,N-substituents on DTC congeners.