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.

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; in revised form: 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

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MDPI and ACS Style

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.

AMA Style

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.. Marine Drugs. 2009; 7(4):640-653.

Chicago/Turabian Style

Lebouvier, Nicolas; Jullian, Valérie; Desvignes, Isabelle; Maurel, Séverine; Parenty, Arnaud; Dorin-Semblat, Dominique; Doerig, Christian; Sauvain, Michel; Laurent, Dominique. 2009. "Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.." Mar. Drugs 7, no. 4: 640-653.

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