The mobilization of intracellular cadmium by butyl and amyl esters of meso-2,3-dimercaptosuccinic acid.
The esters of the general structure, [CH(SH)COOR]2, i.e., Di-BDMS, R = CH2CH(CH3)2; Ds-BDMS, R = CH(CH3)CH2CH3; Di-ADMS, R = CH2CH2CH(CH3)2; and D3-ADMS, R = CH(CH2CH3)2 from the reaction of meso-2,3-dimercaptosuccinic acid with isobutyl, sec-butyl, isoamyl, and 3-amyl alcohols, respectively, have been prepared, characterized, and examined as chelating agents for the removal of cadmium from its aged intracellular deposits. All of these compounds depleted cadmium from such deposits and significantly reduced the whole body levels of cadmium. In the case of three (Ds-BDMS, Di-BDMS, and Di-ADMS) of these compounds, the reductions achieved are equal to or greater than that produced by 2,3-dimercapto-1-propanol (BAL) under similar circumstances. None of these compounds caused any redistribution of cadmium to the brain, and two of them (Di-BDMS and Di-ADMS) caused a very much larger reduction in the liver levels of cadmium than BAL. None was as effective as BAL in reducing kidney levels of cadmium. These compounds are not soluble in water and are administered as solutions in peanut oil. A comparison of the behavior of these compounds with others which have been reported to be effective in reducing body burdens of cadmium in chronic cadmium intoxication reveals that they are among the most effective. An analysis of the manner in which mobilizing efficacy changes with structure indicates that higher, purely alkyl analogs are not expected to be superior to these compounds, though other structural variations may be.
Singh
P K
PK
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Jones
M M
MM
Gale
G R
GR
Atkins
L M
LM
Smith
A B
AB
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D004112:Dimercaprol / Q000494:pharmacology; 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; D004112:Dimercaprol; D004113:Succimer