Selenium Derivatives as Promising Therapy for Chagas Disease: In Vitro and In Vivo Studies
Metadatos
Mostrar el registro completo del ítemAutor
Martín Escolano, Rubén; Rosales Lombardo, María José; Sánchez Moreno, Manuel; Marín Sánchez, ClotildeEditorial
American Chemical Society
Materia
Chagas disease Chemotherapy Drug discovery Selenium derivatives Trypanosoma cruzi
Fecha
2021-04-19Referencia bibliográfica
ACS Infect. Dis. 2021, 7, 6, 1727–1738. [https://doi.org/10.1021/acsinfecdis.1c00048]
Patrocinador
Spanish Government CONSOLIDER CSD2010-00065 CTQ2017-90852-REDC; Alfonso Martin Escudero FoundationResumen
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.