Thiazolidine prodrugs as protective agents against γ-radiation-induced toxicity and mutagenesis in V79 cells

B. H. Wilmore, Pamela Cassidy, R. L. Warters, J. C. Roberts

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Representatives of two classes of thiazolidine prodrug forms of the well-known radioprotective agents L-cysteine, cysteamine, and 2-[(aminopropyl)amino]ethanethiol (WR-1065) were synthesized by condensing the parent thiolamine with an appropriate carbonyl donor. Inherent toxicity of the prodrugs was assessed in V79 cells using a clonogenic survival assay. Protection against radiation-induced cell death was measured similarly after exposure to 0-8 Gy γ (137Cs) radiation. Antimutagenic activity was determined at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus. All thiazolidine prodrugs exhibited less toxicity than their parent thiolamines, sometimes dramatically so. Protection against radiation-induced cell death was observed for the 2-alkylthiazolidine, 2(R,S)-D-ribo-(1′,2′,3′,4′-tetrahydroxybutyl) thiazolidine (RibCyst), which produced a protection factor at 8 Gy of 1.8; the cysteine analogue, 2(R,S)-D-ribo-(1′,2′,3′,4′-tetrahydroxybutyl) thiazolidine-4(R)-carboxylic acid (RibCys), was less active. RibCyst also exhibited excellent antimutational activity, rivaling that of WR-1065. The 2-oxothiazolidine analogues showed little activity in either determination under the conditions tested, perhaps due to their enhanced chemical and biochemical stability.

Original languageEnglish (US)
Pages (from-to)2661-2666
Number of pages6
JournalJournal of Medicinal Chemistry
Volume44
Issue number16
DOIs
StatePublished - Aug 2 2001
Externally publishedYes

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Radiation-Protective Agents
Thiazolidines
Protective Agents
Mutagenesis
Prodrugs
Toxicity
Cysteamine
Radiation Protection
Radiation
Radiation protection
Cysteine
Cell Death
Cell death
Hypoxanthine Phosphoribosyltransferase
Radiation Dosage
Carboxylic Acids
Assays
RibCyst
WR 1065

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Thiazolidine prodrugs as protective agents against γ-radiation-induced toxicity and mutagenesis in V79 cells. / Wilmore, B. H.; Cassidy, Pamela; Warters, R. L.; Roberts, J. C.

In: Journal of Medicinal Chemistry, Vol. 44, No. 16, 02.08.2001, p. 2661-2666.

Research output: Contribution to journalArticle

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