Selective removal of cadmium from aged hepatic and renal deposits: N-substituted talooctamine dithiocarbamates as cadmium mobilizing agents.
The preparation and examination of three dithiocarbamates derived from N-substituted D-gluco-L-talooctamine reveals that the 4-methoxybenzyl derivative (MeOBGD) is superior to any previously prepared dithiocarbamates as an agent for the mobilization of aged intracellular hepatic cadmium deposits from mice. All of these compounds are also quite effective in reducing whole body burdens of cadmium. The use of these compounds does not result in any increase in the cadmium content of the brain. The selection of these chelating agents for synthesis was suggested by an analysis of the log dose-response curves for the mobilization of renal cadmium by previously studied dithiocarbamates. This revealed that the slope of the percentage renal cadmium mobilized vs the log dosage curve is determined to a considerable extent by the sum of the Hansch pi parameters for the substituents, while the intercept is largely determined by the molecular weight of the compound. The implication of such a correlation is that the ability of a chelating agent to remove cadmium from its aged deposits is determined to some extent by its molecular weight, provided the polarity of the overall molecule is appropriate.
Singh
P K
PK
Department of Chemistry, Vanderbilt University, Nashville, TN 37235.
Jones
S G
SG
Gale
G R
GR
Jones
M M
MM
Smith
A B
AB
Atkins
L M
LM
D000375:Aging; D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002106:Cadmium Radioisotopes; D002614:Chelating Agents; D006601:Hexoses; D007202:Indicators and Reagents; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D011865:Radioisotope Dilution Technique; D012545:Schiff Bases; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology*
D002106:Cadmium Radioisotopes; D002614:Chelating Agents; D006601:Hexoses; D007202:Indicators and Reagents; D012545:Schiff Bases; D013859:Thiocarbamates; D002104:Cadmium; C063693:glucotalooctamine