Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.
Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.
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DOI：
10.1016/j.bmc.2006.02.026
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发表时间：
2006-07-01
影响因子：
3.5
通讯作者：
Sauvain, Michel
中科院分区：
文献类型：
--
作者：
Laurent, Dominique;Jullian, Valerie;Sauvain, Michel
作为我们寻找新的抗疟疾药物的一部分，我们在南太平洋海绵中筛选了Pfnek-1的抑制剂，Pfnek-1是恶性疟原虫的一种蛋白激酶。在初步筛选的基础上，选择了在瓦努阿图收集的Xestospongia的一个新种的乙醇粗提物，因为它具有很好的活性。生物测定引导的分级分离使我们分离出抑制Pfnek-1的雄醌，其IC 50约为1 μ M。在一小组疟原虫蛋白激酶中，xestoquinone对PfPK 5显示出适度的蛋白激酶抑制活性，对PfPK 7和PfGSK-3没有活性。Xestoquinone显示出对FCB 1恶性疟原虫菌株的体外抗疟原虫活性，IC 50为3 μ M，选择性指数较弱（SI 7）。在伯氏疟原虫NK 65感染的小鼠中，5 mg/kg的雄甾醌表现出较弱的体内活性，并且在较高剂量下具有毒性。(c)2006爱思唯尔有限公司保留所有权利。
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.