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Enzyme-specific Inhibition of human Glutathione transferases by Dinitronaphthalene derivatives

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dc.contributor.advisor Josephy, David Groom, Hilary 2014-09-03T16:53:09Z 2014-09-03T16:53:09Z 2014-08 2014-08-25 2014-08-25
dc.description.abstract The enzyme glutathione transferase (GST) superfamily catalyzes the detoxication of many xenobiotics and byproducts of aerobic metabolism. GSTs catalyze the conjugation of glutathione with reactive functional groups of xenobiotics. Overexpression of GSTs can contribute to drug and apoptosis resistance in cancer cells and this has motivated research to develop GST inhibitors as adjuvants to chemotherapies. 1-Chloro-2,4-dinitrobenzene (CDNB) is one of the most commonly used substrates for GST activity assays. This project focuses on the interactions of naphthalene congeners of CDNB with recombinant human GST enzymes (Alpha, Mu, and Pi classes). Several dinitronaphthalene derivatives were found to be GST inhibitors. 1-Chloro-2,4-dinitronaphthalene was not a GST substrate, but inhibited the CDNB conjugation activity of GST enzymes. The mechanism of inhibition occurs by formation of a dead-end intermediate Meisenheimer complex in the enzyme active site. Significant mutagenic and toxic effects of these dinitronaphthalene derivatives were observedby conducting Salmonella Ames assays. en_US
dc.description.sponsorship NSERC en_US
dc.language.iso en en_US
dc.publisher Archives of Biochemistry and Biophysics en_US
dc.subject Glutathione transferase en_US
dc.subject Dinitronaphthalene en_US
dc.subject Inhibitors en_US
dc.subject Meisenheimer complex en_US
dc.subject 1-chloro-2,4-dinitrobenzene en_US
dc.title Enzyme-specific Inhibition of human Glutathione transferases by Dinitronaphthalene derivatives en_US
dc.type Article en_US Molecular and Cellular Biology en_US Master of Science en_US Department of Molecular and Cellular Biology en_US
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dcterms.relation Groom H., Lee M., Patil P. & Josephy P.D. (2014) Arch.Biochem.Biophys. 555-556, 71-76

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