Antiparasitic chemotherapy

Three types of potential targets for antiparasitic chemotherapy can be discerned. Firstly, enzymes unique for the parasite could be present. Secondly, enzymes for which alternative pathways exist in the host may be targeted. And thirdly, in principle similar biochemical functions for parasite and host can differ enough to provide, if pharmacologically influenced, some selectivity. Apart from these three types of mechanisms there are antiparasitic agents for which the mechanism has not been identified. 

Ullman B, Allen . Hypoxanthine-guanine phosphoribosyltransferase in trypanosomatids a rational target for antiparasitic chemotherapy. In Boothroyd J, ed. Molecular Approaches to Parasitology. New York Wiley-Liss, Inc., 1995 123-141. 

Katzung PHARMACOLOGY, 9e > Section VIII. Chemotherapeutic Drugs > Chapter 52. Basic Principles of Antiparasitic Chemotherapy > ... 

A rational approach to antiparasitic chemotherapy requires comparative biochemical and physiologic investigations of host and parasite to discover differences in essential processes that... 

Because of the many metabolic deficiencies among parasites resulting from the unique environments in which parasites live in their hosts, there are enzymes whose functions may be essential for the survival of the parasites, but the same enzymes are not indispensable to the host— ie, the host may be able to survive the complete loss of these enzyme functions by achieving the same result through alternative pathways. This discrepancy opens up opportunities for antiparasitic chemotherapy, though insufficiently selective inhibition of parasite enzymes remains an important safety concern. 

Wang, C. C., Parasite Enzymes as Potential Targets for Antiparasitic Chemotherapy, J. Med. Chem. 27 1,1984. 

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Rational approaches to antiparasite chemotherapy utilize the principle of selective toxicity, which exploits biochemical and physiologic differences between parasite and host cells. Many antiparasitic agents target enzymes that are unique to—or indispensable to— parasites other drugs affect cellular functions common to both host and parasite cells (Table 52-2). 

The potential of the purine phosphoribosyl transferases (APRTase, XPRTase, HGPRTase) and AdK as targets for antiparasitic chemotherapy stems from the major role of these enzymes in purine acquisition by the trypanosomatid parasites. However, because of the existence of various alternative purine salvage pathways (Fig. 1), it is conceivable that inhibition of a single enzyme would not kill the parasite. This has been confirmed by elaborate genetic investigation... 

Introduction - The background of parasitism in today s world and the current status of antiparasitic chemotherapy has been outlined in the first four volumes of these reports. Information on new and potential compounds against human and animal parasitoses will be presented in the same chapter this year. 

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