Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a vanuatu marine sponge Pseudoceratina sp.

Nicolas Lebouvier, Valérie Jullian, Isabelle Desvignes, Séverine Maurel, Arnaud Parenty, Dominique Dorin-Semblat, Christian Doerig, Michel Sauvain, Dominique Laurent

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

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 IC 50 around 1.8 μM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC 50 = 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.

Original languageEnglish
Pages (from-to)640-653
Number of pages14
JournalMarine Drugs
Volume7
Issue number4
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

Keywords

  • Homogentisic acid derivatives
  • Pfnek-1
  • Plasmodium falciparum
  • Pseudoceratina

Cite this