The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum.
Bioorg Chem
; 75: 217-223, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28987877
ABSTRACT
The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50=2µM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Proteínas Quinases
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Proteínas de Protozoários
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Emodina
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2017
Tipo de documento:
Article