Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Marine Drugs 640-653 Pseudoceratina Pfnek-1 homogentisic acid derivatives Plasmodium falciparum 2009 fdi:010049155 ENG Marine Drugs 1660-3397 ISI:000273042200013 4 10.3390/md7040640 https://www.documentation.ird.fr/hor/fdi:010049155 https://www.documentation.ird.fr/intranet/publi/2010/01/010049155.pdf 7 Horizon (IRD) 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 mu M. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC50 = 12 mu M). 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. 052 ; 035 UR152