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

Marine Drugs

Nicolas Lebouvier²  Valérie Jullian³  Isabelle Desvignes²  Séverine Maurel³  Arnaud Parenty²  Dominique Dorin-Semblat¹  Christian Doerig¹  Michel Sauvain³ 

[1] INSERM U609, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland; E-Mails:;Laboratoire de Chimie, Université de la Nouvelle-Calédonie, BP R4, 98851 Nouméa cedex, New Caledonia; E-Mails:;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; E-Mails:

关键词: Pseudoceratina;    Pfnek-1;    homogentisic acid derivatives;    Plasmodium falciparum;   

DOI  :  10.3390/md7040640

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland