The challenge of Chagas' disease chemotherapy: an update of drugs assayed against Trypanosoma cruzi.
The chemotherapy of Chagas' disease remains an unsolved problem, and the search for alternative drugs continues. Only two nitroheterocyclic drugs are in clinical use at the present time, and these have severely restricted applicability for chronic patients, as well as being highly toxic. This review covers drugs tested in the last 12 years. A large number of different compounds have been assayed in a variety of ways, most commonly in terms of their capacity to inhibit epimastigote proliferation. Allopurinol has emerged for the treatment of chronic cases. However, only with greater knowledge of the biochemistry of the parasite and in particular of its peculiarities, will it be possible to shift the emphasis of drug research away from random screenings onto a more rational footing. This is exemplified by recent studies carried out using purine derivatives and trypanothione reductase inhibitors.
de Castro
S L
SL
Departamento de Ultraestrutura e Biologia Celular, Instituto Oswaldo Cruz, Fundaçào Oswaldo Cruz, Rio de Janeiro, Brazil.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001393:Azoles / Q000494:pharmacology / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy*; D006801:Humans; D009547:Nifurtimox / Q000494:pharmacology / Q000627:therapeutic use; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001393:Azoles; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole