Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis.
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 techniques. 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.
Werbovetz
K A
KA
Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307, USA. karl.werbovetz@na.amedd.army.mil
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D010961:Plasmodium / Q000187:drug effects / Q000502:physiology; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014345:Trypanosoma / Q000187:drug effects / Q000502:physiology
D000962:Antimalarials; D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents