A plethora of targets, a paucity of drugs: progress towards the development of novel chemotherapies for human African trypanosomiasis.
Human African trypanosomiasis is a major health problem in large regions of Africa. Current chemotherapeutic options are limited and far from ideal. A diverse range of drug targets has been identified and validated in trypanosomes. These include several organelles (glycosomes, acidocalcisomes, kinetoplast) that are not represented in the mammalian host and biochemical pathways that differ significantly from host counterparts (carbohydrate metabolism, protein and lipid modification, response to oxidative stress, cell cycle). However, there has been little progress in developing novel drugs. Pharmaceutical companies are unwilling to invest in the development of drugs for a market that comprises some of the worlds poorest people. This review highlights some of the most attractive drug targets in trypanosomes.
Naula
Christina
C
Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow, UK.
Burchmore
Richard
R
D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002453:Cell Cycle / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D050356:Lipid Metabolism; D017368:Protein Prenylation; D017382:Reactive Oxygen Species; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors
D017382:Reactive Oxygen Species; D014344:Trypanocidal Agents; D025262:Vacuolar Proton-Translocating ATPases; D002118:Calcium