The synthesis and study of novel selenazolidines: potential cancer chemopreventive agents.

Update item information
Publication Type thesis
School or College College of Pharmacy
Department Medicinal Chemistry
Author Short, Megan D.
Title The synthesis and study of novel selenazolidines: potential cancer chemopreventive agents.
Date 2001-05
Description Selenium-containing compounds have been studied extensively for their cancer chemo-preventive properties. Although many of these drugs, such as sodium selenite or 1,4-phenylenebis(methylene)selenocyanate(p-XSC), have shown promise as anticancer agents, the toxicity of such compounds limits their usefulness. A selenocysteine prodrug is proposed to supply selenium in a less toxic manner by utilizing selenocysteine beta-lyase to provide selenium in a biochemically available form. This prodrug approach would overcome the instability and potential toxicity associated with selenocysteine alone, but allows slow release of the active component to proved chemoprevention. A novel prodrug of selenocysteine, 2-oxoselenazolidine-4-carboxylic acid (OSCA), was synthesized and preliminary biological data collected utilizing Chinese hamster lung fibroblast cells. Toxicity data collected on both the L- and D- isomers of OSCA showed a significant reduction in cytotoxicity as compared with the parent compound, selenocysteine. OSCA was also less toxic than other selenium-containing compounds such as sodium selenite, sodium selenite, selenomethionine and p-XSC. Studies were conduced to determine if OSCA released the active component, selenocysteine. Enzymatic hydrolysis studies of OSCA with 5-oxoprolinase were attempted, but were not successful. Additionally, non-enzymatic studies were carried out and compared with the sulfur-containing compounds, 2-thiazolidine-4-carboxylic acid (OTCA). As expected OSCA showed no significant hydrolysis under physiological condition, much like OTCA. Finally, glutathione peroxidase induction (GSH-Px) was studied to determine if OSCA provided selenium in a biochemically available form. The results were compared to sodium selenite and p-XSC. Neither L- or D-OSCA showed induction of GSH-Px in preliminary studies. In conclusion, these studies provide evidence that prodrug forms of selenocysteine can reduce toxicity commonly associated with selenium-containing compounds. However, further investigation is warranted to determine their effectiveness at providing selenium for protein synthesis or other metabolic pathways that may provide cancer chemo-preventive effects.
Type Text
Publisher University of Utah
Subject Metabolism; Chemotherapy
Subject MESH Selenium; Neoplasms
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "The synthesis; and study of novel selenazolidines: potential cancer chemopreventive agents." Spencer S. Eccles Health Sciences Library. Print version of "The synthesis; and study of novel selenazolidines: potential cancer chemopreventive agents." available at J. Willard Marriott Library Special Collection.
Rights Management © Megan D. Short.
Format Medium application/pdf
Identifier us-etd2,3495
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Huntsman Cancer Institiue, the Cancer Research Foundation of American, the Univesrsity of Utah Research Committee, and a NIH gran 1 S10 RRO0626 and CNI grant 5 P30 CA42014.
ARK ark:/87278/s6446224
Setname ir_etd
Date Created 2012-04-23
Date Modified 2012-04-23
ID 193360
Reference URL https://collections.lib.utah.edu/ark:/87278/s6446224