Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.
Laurent Dominique, Jullian Valérie, Parenty Arnaud, Knibiehler Martine, Dorin Dominique, Schmitt Sophie, Lozach Olivier, Lebouvier Nicolas, Frostin Maryvonne, Alby Frédéric, Doerig Christian, Meijer Laurent, Sauvain Michel. 2006. .
ARTICLE, (2006 ) - PUBLISHEDVERSION - English (en-GB)
OPENACCESS -
.
Audience : OTHER
HAL CCSD, Elsevier
Subject
Xestoquinone, Antiplasmodial drug, Antimalarial drug, Plasmodium, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Domains
Santé, Biologie, Médecine
Description
As part of our search for new antimalarial drugs, we have screened for inhibitors of Pfnek-1, a protein kinase of Plasmodium falciparum, in south Pacific marine sponges. On the basis of a preliminary screening, the ethanolic crude extract of a new species of Xestospongia collected in Vanuatu was selected for its promising activity. A bioassay-guided fractionation led us to isolate xestoquinone which inhibits Pfnek-1 with an IC(50) around 1 microM. Among a small panel of plasmodial protein kinases, xestoquinone showed modest protein kinase inhibitory activity toward PfPK5 and no activity toward PfPK7 and PfGSK-3. Xestoquinone showed in vitro antiplasmodial activity against a FCB1 P. falciparum strain with an IC(50) of 3 microM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses.
Creators
Laurent, Dominique, Jullian, Valérie, Parenty, Arnaud, Knibiehler, Martine, Dorin, Dominique, Schmitt, Sophie, Lozach, Olivier, Lebouvier, Nicolas, Frostin, Maryvonne, Alby, Frédéric, Doerig, Christian, Meijer, Laurent, Sauvain, Michel
Contributors
Pharmacochimie des substances naturelles et pharmacophores redox ; Université Toulouse III - Paul Sabatier (UT3) ; Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Insulaire du Vivant et de l'Environnement (LIVE) ; Université de la Nouvelle-Calédonie (UNC), UMS 2646 Pierre Fabre-CNRS, Institut de Sciences et Technologies du Médicament de Toulouse, 3, rue des satellites, 31400 Toulouse, France ; Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre) ; PIERRE FABRE-PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum ; Institut National de la Santé et de la Recherche Médicale (INSERM), Station biologique de Roscoff [Roscoff] (SBR) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), National Science Grant from ACI Pal+ from Research Ministry of France Grant from the EEC (FP6-2002-Life Sciences & Health, PRO-KINASE Research Project)
Sources
ISSN: 0968-0896, EISSN: 1464-3391, Bioorganic and Medicinal Chemistry, https://hal.archives-ouvertes.fr/hal-00090890, Bioorganic and Medicinal Chemistry, Elsevier, 2006, 14(13), pp.4477-4482
