Target-Based Drug Discovery for Malaria, Leishmaniasis, and Trypanosomiasis

摘要

Advances in combinatorial chemistry, high-throughputnscreening, and molecular modeling have revolutionized the process of drugndiscovery in the pharmaceutical industry. Drug discovery efforts for thenprimary protozoal parasitic diseases of the developing world, malaria,nleishmaniasis, and trypanosomiasis, have also begun to employ these tech-nniques. Drug targets in these parasites, exemplified by cysteine proteases and trypanothionenreductase, have been purified and used for inhibitor screening. Through this work, smallnmolecules have been identified that inhibit both parasite proteins and the growth of thenorganisms. This review describes advances that have been made in examining the effects ofnsmall molecules on potential parasitic drug targets determined by biochemical and computer-nbased screening, and also details the activity of such compounds on parasites in vitro and innvivo. Based on these results, it is apparent that modern drug discovery techniques hold promisenfor the identification of antiparasitic drug candidates.