Esters of meso-dimercaptosuccinic acid as cadmium-mobilizing agents.
The dimethyl, diethyl, di-n-propyl, diisopropyl (Di-PDMS), and di-n-butyl esters of meso-2,3-dimercaptosuccinic acid were prepared by esterification of the parent acid and were subsequently purified and characterized. Their relative ability to mobilize cadmium from its aged (greater than 30 days) deposits was evaluated in mice in comparison with 2,3-dimercapto-1-propanol (BAL). All but the dimethyl ester were superior to BAL in reducing the hepatic cadmium levels, though none was superior in reducing renal cadmium levels. Their efficacy in reducing hepatic cadmium levels had the result that all except the dimethyl ester were significantly more effective than BAL in reducing total cadmium body burdens in mice. The most effective of these compounds, Di-PDMS, caused a reduction of whole body cadmium of 59% (i.e., to 41% of control values) under conditions where the corresponding reduction found for BAL was only 18% (i.e., to 82% of control value). The predominant route of excretion of cadmium subsequent to administration of these compounds is via the fecal route (greater than 99%). A synergistic effect was found in the reduction of whole body and kidney cadmium burdens when Di-PDMS was used in combination with trisodium calcium diethylenethriaminepentaacetate.
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; D001812:Blood-Brain Barrier; D001822:Body Burden; D002104:Cadmium / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D004113:Succimer / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D002104:Cadmium; D004113:Succimer