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4,9‐Diaminoacridines and 4‐Aminoacridines as dual‐stage antiplasmodial hits

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Detalhes bibliográficos
Resumo:Multi-stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine-based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine-sensitive and -resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual-stage antiplasmodial hits.
Autores principais:Fonte, Mélanie
Outros Autores:Tassi, Natália; Fontinha, Diana; Bouzón‐Arnáiz, Inés; Ferraz, Ricardo; Araújo, Maria J.; Fernàndez‐Busquets, Xavier; Prudêncio, Miguel; Gomes, Paula; Teixeira, Cátia
Assunto:Plasmodium Acridines Antimalarial activity Blood-stage Liver-stage Malaria Synthesis
Ano:2020
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Multi-stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine-based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine-sensitive and -resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual-stage antiplasmodial hits.