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Differential inhibition of high and low Mr thioredoxin reductases of parasites by organotelluriums supports the concept that low Mr thioredoxin reductases are good drug targets
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2009 (English)In: Parasitology, ISSN 0031-1820, E-ISSN 1469-8161, Vol. 136, no 1, 27-33 p.Article in journal (Refereed) Published
Abstract [en]

Thioredoxin reductase (TrxR), a NADPH-dependent disulfide oxidoreductase, is vital in numerous cellular processes including defence against reactive oxygen species, cell proliferation and signal transduction. TrxRs occur in 2 forms, a high M-r enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low M-r form is present in bacteria, fungi, plants and some protozoan parasites. Our hypothesis is that the differences between the forms can be exploited in the development of selective inhibitors. In this study, cyclodextrin- and sulfonic acid-derived organotelluriums known to inhibit mammalian TrxR were investigated for their relative efficacy against P. falciparum TrxR (PfTrxR), a high M-r enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low M-r form of TrxR. The results suggest that selective inhibition of low M-r TrxRs is a feasible goal.

Place, publisher, year, edition, pages
2009. Vol. 136, no 1, 27-33 p.
Keyword [en]
inhibition, thioredoxin system, malaria, organotellurium compounds, Trichomonas, Plasmodium
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-119658DOI: 10.1017/S0031182008005131ISI: 000262770000003PubMedID: 18980703OAI: oai:DiVA.org:uu-119658DiVA: diva2:300610
Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2011-02-02Bibliographically approved

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