Thiazolidine Prodrugs as Protective Agents against γ-Radiation-Induced Toxicity and Mutagenesis in V79 Cells

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...