Discovery of antiplasmodial pyridine carboxamides and thiocarboxamides.
Int J Parasitol Drugs Drug Resist
; 25: 100536, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38663046
ABSTRACT
Malaria continues to be a significant burden, particularly in Africa, which accounts for 95% of malaria deaths worldwide. Despite advances in malaria treatments, malaria eradication is hampered by insecticide and antimalarial drug resistance. Consequently, the need to discover new antimalarial lead compounds remains urgent. To help address this need, we evaluated the antiplasmodial activity of twenty-two amides and thioamides with pyridine cores and their non-pyridine analogues. Twelve of these compounds showed in vitro anti-proliferative activity against the intraerythrocytic stage of Plasmodium falciparum, the most virulent species of Plasmodium infecting humans. Thiopicolinamide 13i was found to possess submicromolar activity (IC50 = 142 nM) and was >88-fold less active against a human cell line. The compound was equally effective against chloroquine-sensitive and -resistant parasites and did not inhibit ß-hematin formation, pH regulation or PfATP4. Compound 13i may therefore possess a novel mechanism of action.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Piridinas
/
Antimaláricos
Limite:
Humans
Idioma:
En
Revista:
Int J Parasitol Drugs Drug Resist
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Jamaica
País de publicação:
Holanda