Abstract
The rapidly developing resistance to drugs used for prophylaxis and treatment of malaria makes the identification of novel drug targets necessary. Glutathione-S-transferase (GST, E.C. 2.5.1.18), an important enzyme of the glutathione (GSH) cycle, is considered to be an essential detoxification enzyme in malarial parasites. Selective inhibition of this enzyme from malarial parasites by various classes of inhibitors may be viewed as a potential chemotherapeutic strategy to combat malaria. Purified GST from Plasmodium yoelii was inhibited by compounds like protoporphyrin IX, cibacron blue, as well as by the GSH depletor menadione. Cytosolic GST was inhibited to varying degrees by each compound. A characteristic inhibitor constant (K i) was obtained for each inhibitor. The possible consequences of selective inhibition of parasitic GST to that of the host are discussed in relation to the chemotherapy of malaria.
References
Ahmad R, Srivastava AK (2007a) Purification and biochemical characterization of cytosolic glutathione-S-transferase from malarial parasites Plasmodium yoelii. Parasitol Res 100:581–588
Ahmad R, Srivastava AK (2007b) Effect of malaria infection on hepatic and splenic glutathione-S-transferase(s) in Swiss albino and db/+ mice: efficacy of mefloquine and menadione in antimalarial chemotherapy. Parasitology 134:931–938
Ahmad R, Srivastava AK, Tripathi RP, Batra S, Walter RD (2007) Synthesis and biological evaluation of potential modulators of malarial glutathione-S-transferase. J Enzyme Inhib Med Chem 22:327–342
Habig HW, Pabst MJ, Jakoby WB (1974) Glutathione-S-transferase(s): the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Harwaldt P, Rahlfs S, Becker K (2002) Glutathione-S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target. Biol Chem 383:821–830
Jakoby WB, Ziegler DM (1990) The enzymes of detoxication. J Biol Chem 265:20715–20718
Liebau E, Bergmann B, Campbell AM, Teesdale-Spittle P, Brophy PM, Lüersen K, Walter RD (2002) The glutathione-S-transferase from Plasmodium falciparum. Mol Biochem Parasitol 124:85–90
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–276
Mansour TE (2002) The search for antiparasitic agents. In: Chemotherapeutic targets in parasites: contemporary strategies. Cambridge University Press, United Kingdom, pp 1–16
Acknowledgements
Financial assistance from the Council for Scientific and Industrial Research (CSIR), New Delhi (India) in the form of Senior Research Fellowship to R. Ahmad and Volkswagen Stiftung, Hannover (Germany) in the form of ad hoc research grant to A.K. Srivastava is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ahmad, R., Srivastava, A.K. Inhibition of glutathione-S-transferase from Plasmodium yoelii by protoporphyrin IX, cibacron blue and menadione: implications and therapeutic benefits. Parasitol Res 102, 805–807 (2008). https://doi.org/10.1007/s00436-007-0836-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-007-0836-9