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

22 Citations (Scopus)

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 - 1984
Externally publishedYes

Fingerprint

Cadmium
Cadmium Chloride
Sodium
Body Burden
Heavy Metals
Toxicity
Kidney
Water
Liver
4-carboxamidopiperidine-N-dithiocarboxylate
4-hydroxypiperidine-N-dithiocarboxylate

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Heterocyclic N-dithiocarboxylates as cadmium antagonists : 4-Hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate. / Gale, G. R.; Atkins, L. M.; Smith, A. B.; Walker, E. M.; Jones, M. M.; Hodge, R. P.

In: Research Communications in Chemical Pathology and Pharmacology, Vol. 43, No. 2, 1984, p. 281-298.

Research output: Contribution to journalArticle

Gale, G. R. ; Atkins, L. M. ; Smith, A. B. ; Walker, E. M. ; Jones, M. M. ; Hodge, R. P. / Heterocyclic N-dithiocarboxylates as cadmium antagonists : 4-Hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate. In: Research Communications in Chemical Pathology and Pharmacology. 1984 ; Vol. 43, No. 2. pp. 281-298.
@article{c0269a461aeb421f81d8376288914cfb,
title = "Heterocyclic N-dithiocarboxylates as cadmium antagonists: 4-Hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate",
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.",
author = "Gale, {G. R.} and Atkins, {L. M.} and Smith, {A. B.} and Walker, {E. M.} and Jones, {M. M.} and Hodge, {R. P.}",
year = "1984",
language = "English (US)",
volume = "43",
pages = "281--298",
journal = "Research Communications in Chemical Pathology and Pharmacology",
issn = "0034-5164",
publisher = "PJD Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Heterocyclic N-dithiocarboxylates as cadmium antagonists

T2 - 4-Hydroxypiperidine- and 4-carboxamidopiperidine-N-dithiocarboxylate

AU - Gale, G. R.

AU - Atkins, L. M.

AU - Smith, A. B.

AU - Walker, E. M.

AU - Jones, M. M.

AU - Hodge, R. P.

PY - 1984

Y1 - 1984

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021359376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021359376&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 281

EP - 298

JO - Research Communications in Chemical Pathology and Pharmacology

JF - Research Communications in Chemical Pathology and Pharmacology

SN - 0034-5164

IS - 2

ER -