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Article

Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study

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Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain
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Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, 38200 La Laguna, Tenerife, Islas Canarias, Spain
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Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Escuela de Doctorado y Estudios de Posgrado, Universidad de La Laguna, Astrofísico Francisco Sánchez, S/N, 38200 La Laguna, Tenerife, Islas Canarias, Spain
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Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206 La Laguna, Tenerife, Islas Canarias, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Marcelo J. Nieto
Pharmaceuticals 2021, 14(6), 552; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060552
Received: 14 April 2021 / Revised: 2 June 2021 / Accepted: 4 June 2021 / Published: 9 June 2021
(This article belongs to the Special Issue Antiparasitics)
The neglected infection known as Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, results in more than 7000 deaths per year, with an increasing number of cases in non-endemic areas such as Europe or the United States. Moreover, with the current available therapy, only two compounds which are active against the acute phase of the disease are readily available. In addition, these therapeutic agents display multiple undesired side effects such as high toxicity, they are expensive, the treatment is lengthy and the resistant strain has emerged. Therefore, there is a need to find new compounds against Chagas disease which should be active against the parasite but also cause low toxicity to the patients. In the present work, the activity of novel acrylonitriles against Trypanosoma cruzi was evaluated as well as the analysis of the physiological events induced in the treated parasites related to the cell death process. Hence, the characteristic features of an apoptosis-like process such as chromatin condensation and mitochondrial membrane potential, among others, were studied. From the 32 compounds tested against the epimastigote stage of T. cruzi, 11 were selected based on their selectivity index to determine if these compounds were able to induce programmed cell death (PCD) in the treated parasites. Furthermore, acrylonitriles Q5, Q7, Q19, Q27 and Q29 were shown to trigger physiological events related in the PCD. Therefore, this study highlights the therapeutic potential of acrylonitriles as novel trypanocidal agents. View Full-Text
Keywords: chemotherapy; Trypanosoma; acrylonitrile; toxicity; Chagas chemotherapy; Trypanosoma; acrylonitrile; toxicity; Chagas
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MDPI and ACS Style

Bethencourt-Estrella, C.J.; Delgado-Hernández, S.; López-Arencibia, A.; San Nicolás-Hernández, D.; Sifaoui, I.; Tejedor, D.; García-Tellado, F.; Lorenzo-Morales, J.; Piñero, J.E. Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study. Pharmaceuticals 2021, 14, 552. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060552

AMA Style

Bethencourt-Estrella CJ, Delgado-Hernández S, López-Arencibia A, San Nicolás-Hernández D, Sifaoui I, Tejedor D, García-Tellado F, Lorenzo-Morales J, Piñero JE. Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study. Pharmaceuticals. 2021; 14(6):552. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060552

Chicago/Turabian Style

Bethencourt-Estrella, Carlos J., Samuel Delgado-Hernández, Atteneri López-Arencibia, Desirée San Nicolás-Hernández, Ines Sifaoui, David Tejedor, Fernando García-Tellado, Jacob Lorenzo-Morales, and José E. Piñero 2021. "Acrylonitrile Derivatives against Trypanosoma cruzi: In Vitro Activity and Programmed Cell Death Study" Pharmaceuticals 14, no. 6: 552. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060552

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