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Mar. Drugs 2009, 7(4), 640-653; doi:10.3390/md7040640
Article

Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.

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1 Laboratoire de Chimie, Université de la Nouvelle-Calédonie, BP R4, 98851 Nouméa cedex, New Caledonia 2 Laboratoire de Pharmacochimie des Substances Naturelles et Pharmacophores Redox, Université de Toulouse, UPS, UMR 152, 118, rte de Narbonne, F-31062 Toulouse cedex 9, France 3 Institut de Recherche pour le Développement (IRD); UMR 152, 118, rte de Narbonne, F-31062 Toulouse cedex 9, France 4 INSERM U609, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland 5 Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, Scotland, UK
* Author to whom correspondence should be addressed.
Received: 19 October 2009 / Revised: 17 November 2009 / Accepted: 23 November 2009 / Published: 23 November 2009
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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 dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.
Keywords: Pseudoceratina; Pfnek-1; homogentisic acid derivatives; Plasmodium falciparum Pseudoceratina; Pfnek-1; homogentisic acid derivatives; Plasmodium falciparum
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lebouvier, N.; Jullian, V.; Desvignes, I.; Maurel, S.; Parenty, A.; Dorin-Semblat, D.; Doerig, C.; Sauvain, M.; Laurent, D. Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.. Mar. Drugs 2009, 7, 640-653.

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