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

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Advances in combinatorial chemistry, high-throughput screening, and molecular modeling have revolutionized the process of drug discovery in the pharmaceutical industry. Drug discovery efforts for the primary protozoal parasitic diseases of the developing world, malaria, leishmaniasis, and trypanosomiasis, have also begun to employ these tech-niques. Drug targets in these parasites, exemplified by cysteine proteases and trypanothione reductase, have been purified and used for inhibitor screening. Through this work, small molecules have been identified that inhibit both parasite proteins and the growth of the organisms. This review describes advances that have been made in examining the effects of small molecules on potential parasitic drug targets determined by biochemical and computer-based screening, and also details the activity of such compounds on parasites in vitro and in vivo. Based on these results, it is apparent that modern drug discovery techniques hold promise for the identification of antiparasitic drug candidates.
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Keywords: anopheles; antileishmanial; antitrypanosomal; combinatorial chemistry; cruzain; cruzi diamine transporter; falcipain inhibitors; glycolytic enzyme; hexose transporter; high throughput screening; lactate dehydrogenase; leishmania; leishmania nucleoside transporters; leishmaniasis; malaria; malarial proteases; molecular modeling; nucleic acid synthesis; parasitic diseases; phosphoribosyltransferases; plasmepsin inhibitors; plasmodium; polyamine derivatives; proteases; rhodesiense; serine oligopeptidase; transporters; trypanopain Tb; trypanosoma brucei; trypanosome transporters; trypanothione reductase; trypansoma cruzi; tubulin

Document Type: Review Article

Publication date: 2000-08-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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