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- Title
Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.
- Authors
Lebouvier, Nicolas; Jullian, Valérie; Desvignes, Isabelle; Maurel, Séverine; Parenty, Arnaud; Dorin-Semblat, Dominique; Doerig, Christian; Sauvain, Michel; Laurent, Dominique
- Abstract
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 IC50 around 1.8 μM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC50 = 12 μM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromoverongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.
- Subjects
PLASMODIUM falciparum; ANTIMALARIALS; PROTEIN kinases; ANTIFIBRINOLYTIC agents; SPONGES (Invertebrates); PSEUDOCERCOSPORELLA; ETHYLENE dibromide; ETHANOLAMINES; BIOLOGICAL assay
- Publication
Marine Drugs, 2009, Vol 7, Issue 4, p640
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md7040640