Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug.
Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug.
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DOI：
10.1093/infdis/jis184
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发表时间：
2012-04-15
期刊：
影响因子：
--
通讯作者：
Prudêncio M
中科院分区：
文献类型：
--
作者：
da Cruz FP;Martin C;Buchholz K;Lafuente-Monasterio MJ;Rodrigues T;Sönnichsen B;Moreira R;Gamo FJ;Marti M;Mota MM;Hannus M;Prudêncio M
疟原虫在能够感染红细胞并引起疟疾症状之前，在宿主的肝细胞中经历临床沉默和强制性的发育阶段。为了克服靶向疟疾肝脏阶段的化合物的稀缺性，我们筛选了1037种现有药物的库，以确定其抑制疟原虫肝脏发育的能力。癸氧喹酯在体外和体内均成为疟原虫肝脏阶段的最强抑制剂。此外，癸氧喹酯杀死寄生虫的复制血液阶段，并对发育中的配子体（负责传播的形式）具有活性。这种药物通过选择性和特异性地抑制寄生虫的线粒体bc1复合体而起作用，与抗疟药阿托伐醌几乎没有交叉耐药性。口服单剂量癸氧喹酯可有效预防疾病的出现，从而避免将其开发为有效的抗疟化合物。
Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial bc1 complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound.
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DOI：
10.1073/pnas.1104063108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Klonis, Nectarios;Crespo-Ortiz, Maria P.;Tilley, Leann
通讯作者：
Tilley, Leann
影响因子：
3.4
作者：
Prudencio, Miguel;Rodrigues, Cristina D.;Mota, Maria M.
通讯作者：
Mota, Maria M.
影响因子：
64.8
作者：
Gamo, Francisco-Javier;Sanz, Laura M.;Garcia-Bustos, Jose F.
通讯作者：
Garcia-Bustos, Jose F.
影响因子：
5.6
作者：
Bower, MJ;Cohen, FE;Dunbrack, RL
通讯作者：
Dunbrack, RL
DOI：
10.4269/ajtmh.1996.54.62
发表时间：
1996-01-01
影响因子：
3.3
作者：
Looareesuwan, S;Viravan, C;Canfield, CJ
通讯作者：
Canfield, CJ