Structure-activity relationships for in vivo cadmium mobilization by dithiocarbamates derived from lactose and maltotriose.
The relationships between chemical structure and the relative ability to mobilize cadmium in vivo from its aged renal and hepatic deposits have been examined in a series of newly synthesized dithiocarbamates derived from lactose and maltotriose. The results suggest that, in the selection of hydrophobic groups to counter the hydrophilicity contributed by the disaccharides, aromatic groups provide compounds which have a superior efficacy to compounds containing aliphatic groups. The compounds derived from trisaccharides are much less effective than those derived from disaccharides, suggesting that there is a practical size limit to the hydrophilic groups which can be used in the structures of such compounds. With both di- and trisaccharides, aliphatic derivatives with straight chains containing more than eight carbon atoms tend to be less effective than the ones with seven or fewer carbon atoms in the alkyl chain. The three compounds prepared from lactose which contain a benzyl or a methyl-substituted benzyl group are the most effective compounds reported to date for the reduction of whole-body cadmium levels.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Singh
P K
PK
James
S G
SG
Gale
G R
GR
Atkins
L M
LM
Smith
A B
AB
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D007785:Lactose / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000494:pharmacology*; D014312:Trisaccharides / Q000494:pharmacology*
D013859:Thiocarbamates; D014312:Trisaccharides; D002104:Cadmium; C008317:maltotriose; D007785:Lactose