Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase
Rubén Martín-Escolano,
Daniel Molina-Carreño,
Javier Martín-Escolano,
Mª Paz Clares,
Cristina Galiana-Roselló,
Jorge González-García,
Nuria Cirauqui,
José M. Llinares,
María José Rosales,
Enrique García-España,
Clotilde Marín
Affiliations
Rubén Martín-Escolano
Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
Daniel Molina-Carreño
Department of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, Spain
Javier Martín-Escolano
Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain
Mª Paz Clares
Instituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, Spain
Cristina Galiana-Roselló
Instituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, Spain
Jorge González-García
Instituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, Spain
Nuria Cirauqui
EMBL Grenoble, 71 Avenue des Martyrs, 38000 Grenoble, France
José M. Llinares
Instituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, Spain
María José Rosales
Department of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, Spain
Enrique García-España
Instituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, Spain
Clotilde Marín
Department of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, Spain
Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6–8 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD.
