Cancer Chemopreventive Action by the Monomethylated Metabolite of Oltipraz
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Authors
Md. Khabir, Uddin
C. Fishbein, James
Issue Date
2023-03-24
Type
Other
Language
en_US
Keywords
Cancer , Chemotherapy , Enzymes
Alternative Title
Abstract
Cancer chemoprevention involves the use of natural or synthetic compounds to reduce the risk of developing cancer or potentially inhibit the carcinogenic process. Oltipraz, 1,, is a member of a class of compounds called dithiolethiones and has been in phase II clinical trials for the prevention of aflatoxin-induced hepatocellular carcinoma. The compounds 8 and 11 have been synthesized to serve as alternative precursors to the monomethylated metabolites, 5 and 6, of the cancer chemopreventive oltipraz, 1, to test whether they possess similar biological activities. They were subsequently characterized by elemental analysis, 1H and 3C NMR spectroscopy, and two-dimensional methods. In the presence of GSH at physiological pH, precursors 8 and 11, decompose rapidly to generate the corresponding monomethylated metabolites, 5 and 6, which have been monitored by UV-visible spectrophotometer and characterized by LC-MS. The corresponding monomethylated metabolites, 5 and 6 are also generated form their oxidized precursors, 12 and 15 in the presence of GSH at physiological pH. Between two monomethylated metabolites, only 5 could be isolated and characterized by 1H and 13C NMR spectroscopy. Treatment with "prodrugs" 8 and 11 for 48h incubation of Hepa 1c1c7 cells in culture media induce the phase 2 enzyme, quinoneoxidoreductase (NQO1) with potencies on par with oltipraz itself.
Description
UB RISE 2023,
Department of Chemistry, College of Science and Society, University of Bridgeport.
Department of Chemistry and Biochemistry, University of Maryland.