Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 14, Issue 13, Pages 4477-4482Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2006.02.026
Keywords
xestoquinone; antiplasmodial drug; antimalarial drug; Plasmodium
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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 mu M. 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 mu M 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. (c) 2006 Elsevier Ltd. All rights reserved.
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