Alisiaquinones and alisiaquinol, dual inhibitors of Plasmodium falciparum enzyme targets from a New Caledonian deep water sponge
Alisiaquinones and alisiaquinol, dual inhibitors of Plasmodium falciparum enzyme targets from a New Caledonian deep water sponge
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DOI：
10.1021/np8000909
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发表时间：
2008-07-01
影响因子：
5.1
通讯作者：
Debitus, Cecile
中科院分区：
文献类型：
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作者：
Desoubzdanne, Denis;Marcourt, Laurence;Debitus, Cecile
从一种新喀里多尼亚深海海绵中分离得到4个新的高萜化合物：alisiaquinones A-C（1-3）和alisiaquinol（4）。通过光谱数据分析确定了它们的结构和相对立体化学。它们与xestoquinone有关，但在四氢呋喃连接处显示出不寻常的取代。他们显示微摩尔范围内的活动，对疟疾的控制，疟原虫激酶Pfnek-1和蛋白质法尼基转移酶的重要性的两个酶的目标，以及对不同的氯喹敏感和耐药株的恶性疟原虫。泽泻醌C对恶性疟原虫表现出亚微摩尔活性，对不同疟原虫株表现出竞争选择性指数。
Four new meroterpenes, alisiaquinones A-C (1-3) and alisiaquinol (4), were isolated from a New Caledonian deep water sponge. Their structures and relative stereochemistry were elucidated by spectroscopic data analysis. They are related to xestoquinone, but showed unusual substitution on a tetrahydrofuran junction. They displayed micromolar range activity on two enzymatic targets of importance for the control of malaria, the plasmodial kinase Pfnek-1 and a protein farnesyl transferase, as well as on different chloroquine-sensitive and -resistant strains of Plasmodium falciparum. Alisiaquinone C displayed a submicromolar activity on P. falciparum and a competitive selectivity index on the different plasmodial strains.