Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action

Cysteine proteases have been identified as promising targets for the develo pment of antiparasitic chemotherapy. An attractive aspect of these enzymes is their widespread importance in both protozoan and helminth parasites of domestic animals and humans. Concerns about the ability to selectively inhi bit parasite proteases without affecting host homologues have been addresse d in recent studies of Trypanosoma cruzi and Plasmodium falciparum. Signifi cant data on half-life, metabolism, pharmacokinetics and safety have been a ccumulated. Differential uptake of proteases by parasitic organisms versus host cells: and relatively less redundancy in parasite protease gene famili es, may be two factors which contribute to the successful treatment of anim al models of infection. (C) 1999 Australian Society for Parasitology Inc. P ublished by Elsevier Science Ltd. All rights reserved.