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

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

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 CS2 in the presence of NaOH. Following isolation and characterization, each dithiocarboxylate (DTC) when added to an aqueous solution of CdCl2 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 CdCl2 along with 1.0 μCi of 109CdCl2 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.

Original languageEnglish (US)
Pages (from-to)281-298
Number of pages18
JournalResearch Communications in Chemical Pathology and Pharmacology
Volume43
Issue number2
StatePublished - Apr 26 1984

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Pharmacology
  • Pharmacology, Toxicology and Pharmaceutics(all)

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