Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a Vanuatu marine sponge Pseudoceratina sp.
Mar Drugs
; 7(4): 640-53, 2009 Nov 23.
Article
en En
| MEDLINE
| ID: mdl-20098604
As part of our search for new antimalarial drugs in South Pacific marine sponges, we have looked for inhibitors of Pfnek-1, a specific protein kinase of Plasmodium falciparum. On the basis of promising activity in a preliminary screening, the ethanolic crude extract of a new species of Pseudoceratina collected in Vanuatu was selected for further investigation. A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC(50) around 1.8 muM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC(50) = 12 muM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Poríferos
/
Inhibidores de Proteínas Quinasas
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Ácido Homogentísico
/
Antimaláricos
Límite:
Animals
Idioma:
En
Revista:
Mar Drugs
Asunto de la revista:
BIOLOGIA
/
FARMACOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Nueva Caledonia
Pais de publicación:
Suiza