RESUMEN

Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has already been reported. As a consequence, novel chemotypes are urgently needed. Herein we report a novel, in vivo active, fast-acting antimalarial chemotype based on a benzimidazole core. This discovery is the result of a medicinal chemistry plan focused on improving the developability profile of an antichlamydial chemical class previously reported by our group.

Asunto(s)

Antimaláricos/síntesis química , Antimaláricos/farmacología , Benzamidas/síntesis química , Benzamidas/farmacología , Bencimidazoles/química , Bencimidazoles/síntesis química , Bencimidazoles/farmacología , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos , Amidas/síntesis química , Amidas/farmacocinética , Amidas/farmacología , Animales , Antimaláricos/farmacocinética , Benzamidas/farmacocinética , Bencimidazoles/farmacocinética , Células Cultivadas , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Femenino , Humanos , Malaria Falciparum , Ratones Endogámicos NOD , Ratones SCID , Modelos Moleculares , Estructura Molecular , Plasmodium falciparum , Relación Estructura-Actividad , Distribución Tisular