期刊
PHARMACEUTICALS
卷 14, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ph14050419
关键词
American trypanosomiasis; chagas disease; chemotherapy; drug discovery; neglected tropical diseases; screening cascade; selenium derivatives; target product profile; Trypanosoma cruzi
资金
- Ministerio de Economia, Industria y Competitividad [CSD2010-00065, CTQ2017-90852-REDC]
- Conserjeria de Economia, Conocimiento, Empresas y Universidad de la Junta de Andalucia [A-CTS-383-UGR18]
- Institute of Tropical Health of University of Navarre (ISTUN), Caixa Foundation, Roviralta and Ubesol. Spain
- Alfonso Martin Escudero Foundation
Chagas disease is a major public health concern worldwide due to globalization, and the current treatments are limited and outdated, highlighting the urgent need for new therapies to be developed. The in vitro and in vivo activities of forty-eight selenium compounds show potential for a new antichagasic agent, with compound 8 demonstrating promising results that outperform benznidazole.
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 well-known 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.
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