Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases
Martínez-Flórez, Alba (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Galizzi, Melina (University of Georgia. Complex Carbohydrate Research Center)
Izquierdo, Luis 1936-2016 (Barcelona Institute for Global Health (ISGlobal))
Bustamante, Juan M. (University of Georgia. Center for Tropical and Emerging Global Diseases.)
Rodriguez, Ana (New York University School of Medicine. Department of Microbiology)
Rodriguez, Fernando (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Rodríguez-Cortés, Alhelí (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Alberola, Jordi (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)

Data:	2020
Resum:	Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum : dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Bionergetic modulators ; Protozoan parasites ; Repurposing ; Sirolimus ; Dichloroacetate ; 3-bromopyruvate ; 2-deoxy-D-glucose ; Lonidamine ; Metformin
Publicat a:	International Journal for Parasitology: Drugs and Drug Resistance, Vol. 14 (july 2020) , p. 17-27, ISSN 2211-3207

DOI: 10.1016/j.ijpddr.2020.07.002
PMID: 32829099

11 p, 3.3 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
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