Trypanosoma cruzi targets for new chemotherapeutic approaches.
BACKGROUND
Strategies for development of anti-parasite chemotherapy involve identification of active principles of plants, investigation of drugs already licensed for other pathologies, or validation of specific targets identified within key metabolic pathways.


OBJECTIVE
To review the state of the art of drug targets against Trypanosoma cruzi with emphasis on sterol metabolism, kinetoplast DNA (kDNA) sites, trypanothione reductase, cysteine proteinase, hypoxanthine-guanine phosphoribosyltransferase, dihydrofolate reductase and glyceraldehyde-3-phosphate dehydrogenase.


METHODS
Current knowledge, accumulated over the last three decades, on targets for design and development of new trypanocidal compounds is described.


CONCLUSIONS
There is an urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox only allopurinol and a few sterol inhibitors have moved to clinical trials, despite the long list of natural and synthetic compounds assayed against T. cruzi. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity associated with a lack of definitive preclinical evidence of parasitological cure in animal models.
Soeiro
Maria Nazaré C
MN
Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Laboratório de Biologia Celular, Avenue Brazil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. soeiro@ioc.fiocruz.br
de Castro
Solange L
SL
D000818:Animals; D004353:Drug Evaluation, Preclinical; D010427:Pentose Phosphate Pathway; D013261:Sterols / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D013261:Sterols; D014344:Trypanocidal Agents