title: High throughput screening for anti-Trypanosoma cruzi drug discovery.
abstract: 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.
authors.affiliation: New York University School of Medicine, Department of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Julio
authors.initials: J
authors.lastname: Alonso-Padilla
authors.affiliation: New York University School of Medicine, Department of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology*; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051379:Mice; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics
chemical_list: D000981:Antiprotozoal Agents; D016054:DNA, Protozoan