Inhibition of glutathione-S-transferase from Plasmodium yoelii by protoporphyrin IX, cibacron blue and menadione: implications and therapeutic benefits.
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 (Ki) 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.
Ahmad
Rumana
R
Division of Biochemistry, Central Drug Research Institute, Chattar Manzil Palace, P.O. Box No. 173, Lucknow 226001, India.
Srivastava
Arvind K
AK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects / Q000201:enzymology*; D011524:Protoporphyrins / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*; D024483:Vitamin K 3 / Q000494:pharmacology*
D011524:Protoporphyrins; D014227:Triazines; C012842:Cibacron Blue F 3GA; D024483:Vitamin K 3; C028025:protoporphyrin IX; D005982:Glutathione Transferase