Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma Cruzi Mitochondrion
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AuthorMartín-Escolano, Rubén; Molina Carreño, Daniel; Rosales Lombardo, María José; Sánchez Moreno, Manuel; Marín Sánchez, Clotilde
American trypanosomiasisChagas diseaseChemotherapyDrug DiscoveryNeglected tropical diseasesScreening cascadeSelenium derivativesTarget product profileTrypanosoma cruzi
Martín-Escolano, R.; Molina-Carreño, D.; Plano, D.; Espuelas, S.; Rosales, M.J.; Moreno, E.; Aydillo, C.; Sanmartín, C.; Sánchez-Moreno, M.; Marín, C. Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma Cruzi Mitochondrion. Pharmaceuticals 2021, 14, 419. https:// doi.org/10.3390/ph14050419
SponsorshipMinisterio de Economia, Industria y Competitividad, grant number CSD2010–00065 and CTQ2017–90852-REDC; Conserjería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucia, grant number A-CTS-383-UGR18; Institute of Tropical Health of University of Navarre (ISTUN); Caixa Foundation; Roviralta and Ubesol; Alfonso Martín Escudero Foundation
Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the wellknown extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.