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,* email, 2,3email, 1email, 2,3email, 1email, 4,5email, 4,5email, 2,3email and 2,3email
Received: 19 October 2009; in revised form: 17 November 2009 / Accepted: 23 November 2009 / Published: 23 November 2009
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.
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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