Heterocyclic N-dithiocarboxylates as cadmium antagonists: 4-hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate

Journal Article · Wed Feb 01 04:00:00 EST 1984 · Res. Commun. Chem. Pathol. Pharmacol.; (United States)

OSTI ID:7188734

Gale, G R; Atkins, L M; Smith, A B; Walker, Jr, E M; Jones, M M; Hodge, R P

Sodium 4-hydroxypiperidine-N-dithiocarboxylate(HP-N-DTC) and sodium 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC) were synthesized by the reaction of each piperidine analog with CS/sub 2/ in the presence of NaOH. Following isolation and characterization, each dithiocarboxylate (DTC) when added to an aqueous solution of CdCl/sub 2/ formed a water-insoluble complex with Cd which was shown by elemental analyses to consist of DTC:Cd in a 2:1 molar ratio. HP-N-DTC was a highly effective antagonist of acute Cd toxicity in mice, while CAP-N-DTC was less effective. When seven equimolar doses of each DTC were administered to mice which had received a non-lethal dose of CdCl/sub 2/ along with 1.0 microCi of /sup 109/CdCl/sub 2/ 50 days earlier, both effected marked reductions of renal Cd levels. CAP-N-DTC was much more effective than HP-N-DTC in reducing the whole body Cd burden, apparently due to its more rapid depletion of hepatic Cd accompanied by an enhanced rate of Cd excretion. The data illustrate that subtle structural modifications of this class of heavy metal binding agents can yield compounds with impressive differences in pharmacologic activity.

• Research Organization: Veterans Administration Medical Center, Charleston, SC
• OSTI ID: 7188734
• Journal Information: Res. Commun. Chem. Pathol. Pharmacol.; (United States), Journal Name: Res. Commun. Chem. Pathol. Pharmacol.; (United States) Vol. 43:2; ISSN RCOCB
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BODY BURDEN
CADMIUM
CADMIUM 109
CADMIUM ISOTOPES
CHELATING AGENTS
CHEMICAL PREPARATION
CLEARANCE
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
EVEN-ODD NUCLEI
EXCRETION
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METALLOPROTEINS
METALLOTHIONEIN
METALS
MICE
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIPERIDINES
PROTEINS
PYRIDINES
RADIOISOTOPES
RODENTS
SYNTHESIS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES