Synthesis and Preliminary Evaluation of a New Quinuclidine Derivative as a Radioprotective Agent

Shapiro, Warren; Tansy, Martin F.; Elkin, Samuel

doi:10.1002/jps.2600571020

Cited by 7 publications

(2 citation statements)

References 5 publications

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“…The solution was allowed to cool to room temperature and then placed at 4?C overnight. The resulting white solid was isolated by filtration to give 28 Toxicity to V79 cells. Cells (2.5 x 105) were plated into T25 flasks, brought up to a total volume of 5 ml with fresh medium and allowed to adhere overnight.…”

Section: Chemistrymentioning

confidence: 99%

Thiazolidine Prodrugs of Cysteamine and Cysteine as Radioprotective Agents

Roberts¹,

Koch²,

Detrick³

et al. 1995

Radiation Research

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The need for protection against the toxic effects of ionizing radiation comes from many different directions: occupational exposure, nuclear accidents, environmental sources and protection of normal tissue during the therapeutic irradiation of cancer. Sulfhydryl-containing compounds, including cysteamine and L-cysteine, have long been known to possess radioprotective properties, but their therapeutic utility is limited by their side effects at radioprotective doses. To avoid this drawback, thiazolidine prodrugs of cysteamine and L-cysteine were prepared by the condensation of each thioalmine with the aldose monosaccharides, D-ribose and D-glucose, producing RibCyst, GlcCyst, RibCys and GlcCys. The prodrugs were designed to liberate the parent thiolamine nonenzymatically, after ring opening and hydrolysis, which is then available to function as a radioprotective agent. Cysteamine's inherent toxicity, measured using Chinese hamster V79 cells growing in culture, was completely eliminated, even at concentrations as high as 25 mM, by providing the thiolamine in the form of a prodrug. Good protection against radiation-induced lethality was demonstrated by the cysteamine prodrugs using a clonogenic assay. Protection against radiation-induced DNA single-strand breaks, as measured by alkaline elution, was also shown by both RibCyst and GlcCyst; this activity was higher than that exhibited by either cysteamine or WR-1065. The L-cysteine prodrugs, RibCys and GlcCys, also possessed radioprotective abilities under most of the conditions studied. Protection against DNA damage was comparable between L-cysteine, WR-1065 and RibCys.

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Section: Chemistrymentioning

confidence: 99%

Thiazolidine Prodrugs of Cysteamine and Cysteine as Radioprotective Agents

Roberts¹,

Koch²,

Detrick³

et al. 1995

Radiation Research

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“…The pmr spectrum (CDC13) is treated as two separate spectra, the first (interpreted as that of 1) being about four times as intense as the second (considered to be due to 14): 1.28 (t, 3, J = 7 Hz, C/7,CH20), 1.63 (s, 3, CH3C), 2.80 (s, 2?, CH2CO), 2.40-3.73 (m, 5? ), 4.10 ppm (q, 2, J= 7 Hz, CH3C//20); and 1.21 (t, 3,7= 7 Hz, C//3CH20), 1.96 (s, 3, CH3C=C), 2.40-3.73 (m, 5? ), 4.06 (q, 2,7 = 7 Hz, CH3C7/20), 4.48 (s, 1, CH=C), 8.80 ppm (broad, 1?, NH).…”

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confidence: 99%

Radioprotective thiazolidines from .beta.-keto esters

Farmer¹,

Leung²,

Lui³

1973

J. Med. Chem.

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Antiradiation activity has been reported for a variety of thiazolidines,1'7 although the absence of significant protection in certain other derivatives led Sweetman, etal.,s to conclude that a thiazolidine "ordinarily is likely to lock an aminothiol too firmly into a stable structure to afford a promising means of latentiating biologically active aminothiols."We have latentiated the well-known radioprotective 2-mercaptoethylamine (MEA) in the form of 2,2-disubstituted thiazolidine derivatives of some ß-keto esters. The results of preliminary screening of these compounds for antiradiation activity in mice have been presented elsewhere.9 Results and DiscussionData for the compounds prepared are shown in Table I. The synthesis of the thiazolidine bases 1-4 from MEA by a procedure similar to that used by Tondeur, et tú.,10 was

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