Parasite enzymes as potential targets for antiparasitic chemotherapy.

I have thus far listed a total of 10 potential targets for antiparasitic chemotherapeutic consideration. This is by no means a completed list. Many more will be added to it with time and with more future findings. Among these 10 targets (summarized in Table I), however, one may gain some insight and see a few interesting general trends: (1) Nucleic acid metabolism and carbohydrate-energy metabolism in protozoan parasites appear to be targets for fruitful chemotherapeutic attacks. Their being useful targets results generally from the deficient metabolism in the protozoan parasites. Thus, the main vulnerability among the protozoan parasites is closely associated with their parasitic nature. (2) Microtubules and nervous systems appear to be the main chemotherapeutic targets in helminths. They differ from those in the host not because of their parasitic nature but, more likely, because of the evolutionary distance separating the mammalian hosts and the primitive metazoa. Thus, free-living nematodes, such as Caenorhabditis elegans, have their microtubules just as susceptible to the benzimidazole anthelmintics as those from the parasitic worms. The motoneuronal map of C. elegans is identical with that of Ascaris lumbricoides. Both worms are similarly immobilized by levamisole, piperazine, avermectins, etc. The dual insecticidal and antiexoparasite activities found in the avermectins and milbemycins may also suggest that the free-living insects and the ticks and lice may have the same GABA nervous system. This main discrepancy between protozoan parasites and metazoan parasites may be partly attributable to the higher mutation rates and higher frequencies of genetic recombination among the protozoa, evidenced by the higher rates of development of drug resistance among them. The fast adaptation to a new environment may be essential for survival, but it would also lead to metabolic deficiencies after the protozoa lived in a luxurious environment for a while. This revelation may suggest that future chemotherapeutic studies on parasitic helminths can utilize free-living helminths as models to eliminate many unnecessary technical difficulties. Also, there perhaps could be a further classification among the parasites to term the protozoa "true parasites" and the helminth "pseudo-parasites" from the viewpoint of chemotherapy.