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., Westrop, G.D., Coombs, G.H., Engman, L. and Muller, S. (2009) 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. Parasitology, 136(01), pp. 27-33. (doi: 10.1017/S0031182008005131)

Abstract

SUMMARYThioredoxin 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muller, Professor Sylke and Patzewitz, Ms Eva-Maria and Coombs, Professor Graham and McMillan, Dr Paul and Westrop, Mr Gareth
• Authors: McMillan, P.J., Patzewitz, E.-M., Young, S., Westrop, G.D., Coombs, G.H., Engman, L., and Muller, S.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Parasitology
• ISSN: 0031-1820