Trypanosoma cruzi targets for new chemotherapeutic approaches

Abstract

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. Results/conclusion: 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.

Keywords::

• Chagas disease
• chemotherapy
• drug targets
• Trypanosoma cruzi

Acknowledgments

The authors thank the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (APQ1 and Pensa Rio), Conselho Nacional Desenvolvimento Científico e Tecnológico (CNPq), DECIT/SCTIE/MS, PAPESV/FIOCRUZ for projects funding.

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