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

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.

Xestoquinone 1 and halenaquinone 2 were isolated from a Vanuatu marine sponge Xestospongia sp. and tested for their Plasmodium falciparum protein kinase inhibitory activity (Pfnek-1). The antimalarial activity of xestoquinone was assessed in vitro and in vivo.Figure optionsDownload as PowerPoint slide