Trypanocidal drugs: mechanisms, resistance and new targets.
The protozoan parasites Trypanosoma brucei and Trypanosoma cruzi are the causative agents of African trypanosomiasis and Chagas disease, respectively. These are debilitating infections that exert a considerable health burden on some of the poorest people on the planet. Treatment of trypanosome infections is dependent on a small number of drugs that have limited efficacy and can cause severe side effects. Here, we review the properties of these drugs and describe new findings on their modes of action and the mechanisms by which resistance can arise. We further outline how a greater understanding of parasite biology is being exploited in the search for novel chemotherapeutic agents. This effort is being facilitated by new research networks that involve academic and biotechnology/pharmaceutical organisations, supported by public-private partnerships, and are bringing a new dynamism and purpose to the search for trypanocidal agents.
Wilkinson
Shane R
SR
Queen Mary Pre-Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK. s.r.wilkinson@qmul.ac.uk
Kelly
John M
JM
D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D006801:Humans; D009581:Nitrofurans / Q000378:metabolism; D009601:Nitroreductases / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
D009581:Nitrofurans; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D009601:Nitroreductases