Structure-activity relationships for intracellular cadmium mobilization by N-alkyl-4-O-(beta-D-galactopyranosyl)-D-glucamine-N-carbodithioates+ ++.
An examination of a group of dithiocarbamate chelating agents derived from various alkylamines and lactose reveals that the relative potencies in the mobilization of intracellular cadmium from renal and hepatic deposits in mice are highly dependent upon the size and nature of the alkyl groups. For those compounds containing straight-chain alkyl groups, the potency drops off as the number of carbon atoms is increased beyond seven. Branched-chain alkyl groups are more effective in promoting the removal of cadmium than straight-chain alkyl groups with the same number of carbon atoms. The fact that these compounds are effective in the mobilization of intracellular cadmium deposits suggests that the size and shape of the alkyl group are important in the determination of the facility with which the compound can pass through cellular membranes. Straight-chain derivatives with 10 or more carbon atoms were more toxic than those with nine or fewer carbon atoms. Of the new compounds, four (the n-hexyl, n-heptyl, n-octyl, and 2-ethylhexyl derivatives) are more effective than the corresponding benzyl derivative in inducing a reduction of hepatic cadmium levels from animals given cadmium at least 1 week previously. The results obtained indicate that modest modifications in the groups on the basic dithiocarbamate structure can produce agents of significantly enhanced effectiveness for the removal of cadmium from its hepatic deposits.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Singh
P K
PK
Gale
G R
GR
Atkins
L M
LM
Smith
A B
AB
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000494:pharmacology*
D002614:Chelating Agents; D013859:Thiocarbamates; D002104:Cadmium