Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase
Chagas disease (CD) is a tropical and potentially fatal infection caused by <i>Trypanosoma cruzi</i>. 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 effectiv...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/140 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rubén Martín-Escolano |
| collection | DOAJ |
| description | Chagas disease (CD) is a tropical and potentially fatal infection caused by <i>Trypanosoma cruzi</i>. 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 <i>T. cruzi</i>. In short, 16 aryl polyamines were screened in vitro against different <i>T. cruzi</i> 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 <b>15</b> as a potential compound that provides a step forward for the development of new agents to combat CD. |
| first_indexed | 2024-03-09T11:27:37Z |
| format | Article |
| id | doaj.art-78d2aa3daf6e4c9fa410f213f6f2ea95 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-78d2aa3daf6e4c9fa410f213f6f2ea952023-11-30T23:58:17ZengMDPI AGPharmaceutics1999-49232022-12-0115114010.3390/pharmaceutics15010140Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide DismutaseRubén Martín-Escolano0Daniel Molina-Carreño1Javier Martín-Escolano2Mª Paz Clares3Cristina Galiana-Roselló4Jorge González-García5Nuria Cirauqui6José M. Llinares7María José Rosales8Enrique García-España9Clotilde Marín10Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UKDepartment of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, SpainUnit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, SpainInstituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, SpainInstituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, SpainInstituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, SpainEMBL Grenoble, 71 Avenue des Martyrs, 38000 Grenoble, FranceInstituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, SpainDepartment of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, SpainInstituto de Ciencia Molecular (ICMol), Departamento de Química Inorgánica, Universidad de Valencia, 46980 Paterna, SpainDepartment of Parasitology, University of Granada, Severo Ochoa s/n, 18071 Granada, SpainChagas disease (CD) is a tropical and potentially fatal infection caused by <i>Trypanosoma cruzi</i>. 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 <i>T. cruzi</i>. In short, 16 aryl polyamines were screened in vitro against different <i>T. cruzi</i> 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 <b>15</b> as a potential compound that provides a step forward for the development of new agents to combat CD.https://www.mdpi.com/1999-4923/15/1/140chagas diseasechemotherapydrug discoveryaryl polyamines<i>Trypanosoma cruzi</i> |
| spellingShingle | 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 Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase Pharmaceutics chagas disease chemotherapy drug discovery aryl polyamines <i>Trypanosoma cruzi</i> |
| title | Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase |
| title_full | Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase |
| title_fullStr | Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase |
| title_full_unstemmed | Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase |
| title_short | Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase |
| title_sort | identification of aryl polyamines derivatives as anti i trypanosoma cruzi i agents targeting iron superoxide dismutase |
| topic | chagas disease chemotherapy drug discovery aryl polyamines <i>Trypanosoma cruzi</i> |
| url | https://www.mdpi.com/1999-4923/15/1/140 |
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