Publication: Selenium Derivatives as Promising Therapy for Chagas Disease: In Vitro and In Vivo Studies.
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Identifiers
Date
2021-04-19
Authors
Martin-Escolano, Ruben
Etxebeste-Mitxeltorena, Mikel
Martin-Escolano, Javier
Plano, Daniel
Rosales, Maria J
Espuelas, Socorro
Moreno, Esther
Sanchez-Moreno, Manuel
Sanmartin, Carmen
Marin, Clotilde
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Abstract
Chagas disease is a tropical infection caused by the protozoan parasite Trypanosoma cruzi and a global public health concern. It is a paradigmatic example of a chronic disease without an effective treatment. Current treatments targeting T. cruzi are limited to two obsolete nitroheterocyclic drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Hence, new, more effective, safer, and affordable drugs are urgently needed. Selenium and their derivatives have emerged as an interesting strategy for the treatment of different prozotoan diseases, such as African trypanosomiasis, leishmaniasis, and malaria. In the case of Chagas disease, diverse selenium scaffolds have been reported with antichagasic activity in vitro and in vivo. On the basis of these premises, we describe the in vitro and in vivo trypanocidal activity of 41 selenocompounds against the three morphological forms of different T. cruzi strains. For the most active selenocompounds, their effect on the metabolic and mitochondrial levels and superoxide dismutase enzyme inhibition capacity were measured in order to determine the possible mechanism of action. Derivative 26, with a selenocyanate motif, fulfills the most stringent in vitro requirements for potential antichagasic agents and exhibits a better profile than benznidazole in vivo. This finding provides a step forward for the development of a new antichagasic agent.
Description
MeSH Terms
Chagas Disease
Humans
Pharmaceutical Preparations
Selenium
Trypanocidal Agents
Trypanosoma cruzi
Humans
Pharmaceutical Preparations
Selenium
Trypanocidal Agents
Trypanosoma cruzi
DeCS Terms
Enfermedad de chagas
Humanos
Preparaciones farmacéuticas
Selenio
Tripanocidas
Trypanosoma cruzi
Humanos
Preparaciones farmacéuticas
Selenio
Tripanocidas
Trypanosoma cruzi
CIE Terms
Keywords
Chagas disease, Trypanosoma cruzi, chemotherapy, drug discovery, selenium derivatives
Citation
Martín-Escolano R, Etxebeste-Mitxeltorena M, Martín-Escolano J, Plano D, Rosales MJ, Espuelas S, et al. Selenium Derivatives as Promising Therapy for Chagas Disease: In Vitro and In Vivo Studies. ACS Infect Dis. 2021 Jun 11;7(6):1727-1738.