Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.

Dominique Laurent; Valérie Jullian; Arnaud Parenty; Martine Knibiehler; Dominique Dorin; Sophie Schmitt; Olivier Lozach; Nicolas Lebouvier; Maryvonne Frostin; Frédéric Alby; Séverine Maurel; Christian Doerig; Laurent Meijer; Michel Sauvain

doi:10.1016/j.bmc.2006.02.026

Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.

Dominique Laurent
, Valérie Jullian
, Arnaud Parenty
, Martine Knibiehler
, Dominique Dorin
, Sophie Schmitt
, Olivier Lozach
, Nicolas Lebouvier
, Maryvonne Frostin
, Frédéric Alby
, Séverine Maurel
, Christian Doerig
, Laurent Meijer
, Michel Sauvain

Université de Toulouse
Université de Toulouse
UMR ENTROPIE (Institut de Recherche pour le Développement - Université de La Réunion - Université de la Nouvelle-Calédonie - CNRS - IFREMER)
Institut de Sciences et Technologies du Médicament de Toulouse
University of Glasgow
Station Biologique de Roscoff

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

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 IC₅₀ around 1 μM. 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 IC₅₀ of 3 μM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses.

Original language	English
Pages (from-to)	4477-4482
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	14
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2006.02.026
State	Published - 1 Jul 2006
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antimalarial drug
Antiplasmodial drug
Plasmodium
Xestoquinone

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10.1016/j.bmc.2006.02.026

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Laurent, D., Jullian, V., Parenty, A., Knibiehler, M., Dorin, D., Schmitt, S., Lozach, O., Lebouvier, N., Frostin, M., Alby, F., Maurel, S., Doerig, C., Meijer, L., & Sauvain, M. (2006). Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp. Bioorganic and Medicinal Chemistry, 14(13), 4477-4482. https://doi.org/10.1016/j.bmc.2006.02.026

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title = "Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.",

abstract = "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 IC50 around 1 μM. 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 IC50 of 3 μM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses.",

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Laurent, D, Jullian, V, Parenty, A, Knibiehler, M, Dorin, D, Schmitt, S, Lozach, O, Lebouvier, N, Frostin, M, Alby, F, Maurel, S, Doerig, C, Meijer, L & Sauvain, M 2006, 'Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.', Bioorganic and Medicinal Chemistry, vol. 14, no. 13, pp. 4477-4482. https://doi.org/10.1016/j.bmc.2006.02.026

TY - JOUR

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AU - Laurent, Dominique

AU - Jullian, Valérie

AU - Parenty, Arnaud

AU - Knibiehler, Martine

AU - Dorin, Dominique

AU - Schmitt, Sophie

AU - Lozach, Olivier

AU - Lebouvier, Nicolas

AU - Frostin, Maryvonne

AU - Alby, Frédéric

AU - Maurel, Séverine

AU - Doerig, Christian

AU - Meijer, Laurent

AU - Sauvain, Michel

PY - 2006/7/1

Y1 - 2006/7/1

N2 - 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 IC50 around 1 μM. 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 IC50 of 3 μM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses.

AB - 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 IC50 around 1 μM. 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 IC50 of 3 μM and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses.

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KW - Antiplasmodial drug

KW - Plasmodium

KW - Xestoquinone

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U2 - 10.1016/j.bmc.2006.02.026

DO - 10.1016/j.bmc.2006.02.026

M3 - Artículo

C2 - 16513357

AN - SCOPUS:33747343238

SN - 0968-0896

VL - 14

SP - 4477

EP - 4482

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 13

ER -

Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.

Abstract

UN SDGs

Keywords

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