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Experimental models in Chagas disease: a review of the methodologies applied for screening compounds against Trypanosoma cruzi

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Abstract

One of the main problems of Chagas disease (CD), the parasitic infection caused by Trypanosoma cruzi, is the lack of a completely satisfactory treatment, which is currently based on two old nitroheterocyclic drugs (i.e., nifurtimox and benznidazole) that show important limitations for treating patients. In this context, many laboratories look for alternative therapies potentially applicable to the treatment, and therefore, research in CD chemotherapy works in the design of experimental protocols for detecting molecules with activity against T. cruzi. Phenotypic assays are considered the most valuable strategy for screening these antiparasitic compounds. Among them, in vitro experiments are the first step to test potential anti-T. cruzi drugs directly on the different parasite forms (i.e., epimastigotes, trypomastigotes, and amastigotes) and to detect cytotoxicity. Once the putative trypanocidal drug has been identified in vitro, it must be moved to in vivo models of T. cruzi infection, to explore (i) acute toxicity, (ii) efficacy during the acute infection, and (iii) efficacy in the chronic disease. Moreover, in silico approaches for predicting activity have emerged as a supporting tool for drug screening procedures. Accordingly, this work reviews those in vitro, in vivo, and in silico methods that have been routinely applied during the last decades, aiming to discover trypanocidal compounds that contribute to developing more effective CD treatments.

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Funding

The authors thank the Spanish Ministry of Economy, Industry and Competitiveness (MINEICO, ref. SAF2015-66690-R) and the 911120 UCM-CEI Moncloa Research Group “Terapia Antiparasitaria.”

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Authors and Affiliations

  1. Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, 28040, Madrid, Spain

    Cristina Fonseca-Berzal, José A. Escario & Alicia Gómez-Barrio

  2. Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC), c/ Juan de la Cierva 3, 28006, Madrid, Spain

    Vicente J. Arán

Authors
  1. Cristina Fonseca-Berzal
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  2. Vicente J. Arán
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  3. José A. Escario
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  4. Alicia Gómez-Barrio
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Correspondence to Cristina Fonseca-Berzal.

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Fonseca-Berzal, C., Arán, V.J., Escario, J.A. et al. Experimental models in Chagas disease: a review of the methodologies applied for screening compounds against Trypanosoma cruzi. Parasitol Res 117, 3367–3380 (2018). https://doi.org/10.1007/s00436-018-6084-3

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