ABSTRACT
Many parasites including the causative agents of malaria (Plasmodium falciparum) and of Chagas’ heart disease (Trypanosoma cruzi) appear to be more sensitive to oxidative stress than their mammalian hosts. Consequently, we have chosen thiol generating antioxidant enzymes as potential targets for the chemotherapy of these diseases. In the case of malaria we are attempting to develop inhibitors against a host protein, namely erythrocyte glutathione reductase, (NADPH+GSSG+H+ =NADP++2GSH); a flavoprotein whose stereochemistry of catalysis is known in atomic detail. With Chagas’ disease, our target protein is trypanothione reductase of T. cruzi. This enzyme, which appears to occur exclusively in trypanosomatids, catalyses the reduction of glutathionylspermidine disulphides by NADPH.
