Enzymes of parasite thiol metabolism as drug targets.
The potential for chemotherapeutic exploitation of thiol metabolism in parasitic protozoa is reviewed here by Luise Krauth-Siegel and Graham Coombs. The review is based largely on discussions held at a meeting of the COST B9 Action entitled 'Chemotherapy of Protozoal Infections'*. The major questions posed were: which enzymes are the best to target; what further information is required to allow their use for rational drug development; and how can this be achieved most efficiently? Not surprisingly, only partial answers could be obtained in many cases, but the interactive discussion between the multidisciplinary group of participants provided thought-provoking ideas and will help direct future research.
Krauth-Siegel
R L
RL
Biochemie-Zentrum Heidelberg, Ruprecht-Karls-Universität, D-69120 Heidelberg, Germany. krauth-siegel@urz.uni-heidelberg.de
Coombs
G H
GH
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011446:Prospective Studies; D013095:Spermidine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; C044809:trypanothione; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione; D013095:Spermidine