Hemisíntesis de un híbrido diosgenona-artesunato y su efecto antiplasmodial
DOI:
https://doi.org/10.17533/udea.vitae.18823Keywords:
Híbridos antimaláricos, diosgenona, artesunato, malaria, PlasmodiumAbstract
Antecedentes: La malaria es una enfermedad causada por parásitos del género Plasmodium y transmitida por mosquitos de género Anopheles. Anualmente, se reportan alrededor de 220 millones de casos de malaria en el mundo, de los cuales mueren aproximadamente 650.000 personas, convirtiendo esta enfermedad en un problema de salud pública. En los últimos años se ha reportado resistencia de los parásitos a los antimaláricos: cloroquina, mefloquina y recientemente a los derivados de artemisininas, como artesunato. Objetivo: Obtener por hemisíntesis un híbrido de diosgenona-artesunato con un conector hidrolizable tipo éster, y valorar su actividad antiplasmodial y citotoxicidad in vitro. Métodos: Para la obtención del híbrido 4, se redujo el grupo carbonilo de la diosgenona en presencia de borohidruro de sodio, para generar un alcohol, el cual se usó para enlazarse con el artesunato, por medio de una reacción de esterificación promovida por el reactivo de Yamaguchi. La actividad antiplasmodial se determinó en la cepa 3D7 de P. falciparum sensible a cloroquina, la citotoxicidad se evaluó en la línea celular HepG2. Resultados: Mediante una reacción de esterificación con el reactivo de Yamaguchi, se obtuvo el primer híbrido diosgenona-artesunato 4 (IC50=0,0157 μM), el cual fue más activo que la molécula de partida diosgenona 1 (IC50=35,49 μM) y la diosgenona reducida 2 (IC50=46,33 μM) pero no más que el artesunato 3 (IC50 = 0,0020 μM). Conclusiones: Se obtuvo un nuevo híbrido de diosgenona-artesunato el cual presenta mejor actividad que la molécula natural; resultado de importancia para su uso potencial contra cepas resistentes al artesunato.
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References
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