In vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine Mannich base derivatives

Leishmaniasis is one of the world’s most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight Leishma...

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Detalles Bibliográficos
Autores: Martin-Montes, A.(Alvaro)|||/items/df247317-6055-429d-a1a2-f5c3db7144f7, Santivañez-Veliz, M. (Mery)|||/items/9bc967ce-1196-4f0b-a05a-5aca7c220cbb, Moreno-de-Viguri, E. (Elsa)|||/items/08473f69-a6ab-4896-8cf9-41e6daf12bfa, Martin-Escolano, R. (Ruben)|||/items/6e08c426-cb50-4ad7-b8ec-8b1c7be56e56, Jimenez-Montes, C. (Carmen)|||/items/4ceb82d8-e047-4ecb-a3c6-1d45fe1e5175, Lopez-Gonzalez, C. (Catalia)|||/items/6f8bc670-fa09-4846-92f5-d979e9dec1a4, Marin, C. (Clotilde)|||/items/68b0ce8a-9019-4f87-8dbe-f82130d83c2e, Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7, Gutierrez-Sanchez, R. (Ramon)|||/items/247e43e8-fca7-4a4f-bb02-4ad48b4dc15b, Sanchez-Moreno, M. (Manuel)|||/items/1a7934cb-993a-46b7-87a0-39c332e1821d, Pérez-Silanes, S. (Silvia)|||/items/e5734c65-2dd8-4fdd-a74a-fc7526136c45
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/61121
Acceso en línea:https://hdl.handle.net/10171/61121
Access Level:acceso abierto
Palabra clave:Leishmania infantum
Leishmania donovani
Leishmania braziliensis
Iron superoxide dismutase
Arylamine derivatives
Mannich base derivatives
Descripción
Sumario:Leishmaniasis is one of the world’s most neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight Leishmaniasis remains a crucial goal today. With this purpose in mind, we present twenty arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of L. infantum, L. donovani and L. braziliensis strains. Six out of the twenty Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at a IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in glucose catabolism and leading to greater levels of Fe-SOD (iron superoxide dismutase) inhibition. These molecules could be potential candidates for Leishmaniasis chemotherapy.

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