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

P.J. McMillan, E.M. Patzewitz, S.E. Young, G.D. Westrop, G.H. Coombs, L. Engman, S. Muller

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr 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 Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.
Original languageEnglish
Pages (from-to)27-33
Number of pages6
JournalParasitology
Volume136
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

Trichomonas vaginalis
Thioredoxin-Disulfide Reductase
Plasmodium falciparum
Parasites
parasites
drugs
cyclodextrins
sulfonic acid
oxidoreductases
enzymes
sulfides
NADP (coenzyme)
Pharmaceutical Preparations
malaria
Protozoa
signal transduction
reactive oxygen species
cell proliferation
mammals
fungi

Keywords

  • inhibition
  • thioredoxin system
  • malaria
  • organotellurium compounds
  • Trichomonas
  • Plasmodium

Cite this

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title = "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",
abstract = "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 Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr 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 Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.",
keywords = "inhibition, thioredoxin system, malaria, organotellurium compounds, Trichomonas, Plasmodium",
author = "P.J. McMillan and E.M. Patzewitz and S.E. Young and G.D. Westrop and G.H. Coombs and L. Engman and S. Muller",
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language = "English",
volume = "136",
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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. / McMillan, P.J.; Patzewitz, E.M.; Young, S.E.; Westrop, G.D.; Coombs, G.H.; Engman, L.; Muller, S.

In: Parasitology, Vol. 136, No. 1, 2009, p. 27-33.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - McMillan, P.J.

AU - Patzewitz, E.M.

AU - Young, S.E.

AU - Westrop, G.D.

AU - Coombs, G.H.

AU - Engman, L.

AU - Muller, S.

PY - 2009

Y1 - 2009

N2 - 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 Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr 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 Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.

AB - 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 Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr 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 Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.

KW - inhibition

KW - thioredoxin system

KW - malaria

KW - organotellurium compounds

KW - Trichomonas

KW - Plasmodium

UR - http://dx.doi.org/10.1017/S0031182008005131

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