Evaluación de endoperóxidos frente a Leishmania spp.: Avances y perspectivas

Laura Machín Galarza; Lars Gille; Lianet Monzote Fidalgo

Evaluación de endoperóxidos frente a Leishmania spp.: Avances y perspectivas

Laura Machín Galarza, Lars Gille, Lianet Monzote Fidalgo

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Resumen

Introducción: Los endoperóxidos son moléculas que presentan un enlace O-O entre dos átomos de carbono de un anillo cíclico. Aunque se conocen varios ejemplos de estas moléculas, solo se identificaron revisiones de actividad antileishmanial para la artemisina y sus derivados, donde no se consideran los aportes experimentales recientes.

Objetivo: Identificar evidencias recientes de acción antileishmanial de endoperóxidos de diferentes fuentes.

Métodos: Se realizó una revisión de artículos publicados en 10 años (2013-2022), en español e inglés, principalmente en la base de datos PubMed/Medline y utilizando Google Scholar.

Resultados: Tras revisar 44 artículos originales se identificaron 31 endoperóxidos activos sobre Leishmania; de los cuales 11 fueron 1,2,4-trioxanos, 12, 1,2-dioxanos, seis derivados de 2-adamanto, además de dos tetraoxanos. Además de la artemisina y sus derivados, se destacan como compuestos promisorios el ascaridol, por su capacidad de controlar el desarrollo de lesiones cutáneas murinas, y dos tetraoxanos que disminuyeron significativamente la carga parasitaria en hígado y bazo de ratones infectados.

Conclusiones: Las potencialidades farmacológicas de los endoperóxidos frente a Leishmania spp. se ha demostrado en estudios de diferentes grupos de investigación. Los trabajos publicados se han desarrollado fundamentalmente in vitro y en especies de Asia, África y el sur de Europa. Se proponen posibles dianas moleculares mitocondriales, sin descartar la contribución de las membranas, citoplasma y kinetoplasto del parásito al mecanismo de acción. La información reunida puede facilitar el reposicionamiento de las artemisinas y/o la selección de otros endoperóxidos como punto de partida para el desarrollo de una nueva opción terapéutica.

Palabras clave

endoperóxido; Leishmania; artemisina; dioxano; tetraoxano.

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