High throughput screening for anti-Trypanosoma cruzi drug discovery.

The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available ther...

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Bibliographic Details
Published in:PLoS Neglected Tropical Diseases
Main Authors: Julio Alonso-Padilla, Ana Rodríguez
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2014
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0003259
https://doaj.org/article/630f377cae3845999737cfcf6d8bdb2f
Description
Summary:The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti-T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti-T. cruzi drug entities in the near future, are reviewed here.