Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum
Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum
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DOI：
10.1016/j.bcp.2005.07.021
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发表时间：
2005-10-15
影响因子：
5.8
通讯作者：
Tilley, L
中科院分区：
文献类型：
--
作者：
Bray, PG;Deed, S;Tilley, L
近年来，对抗疟药氯喹的抗药性已经普遍存在。因此，迫切需要找到可以替代氯喹或与这种药物协同工作的化合物，以克服氯喹耐药性。我们研究了氯喹（一种4-氨基喹啉）和一些8-氨基喹啉类药物（包括伯氨喹，一种广泛用于治疗间日疟原虫感染的药物）之间的相互作用。我们发现伯氨喹是一种有效的增效剂的活性氯喹抗氯喹恶性疟原虫。对表达恶性疟原虫氯喹抗性转运蛋白（PfCRT）的突变型和野生型等位基因的匹配转染子的分析表明，伯氨喹通过阻断PfCRT发挥其活性，从而增强氯喹积累。我们的数据表明，两种已获准用于人类的抗疟药物的新型制剂可用于治疗氯喹耐药寄生虫。(c)2005年爱思唯尔公司All rights reserved.
In recent years, resistance to the antimalarial drug, chloroquine, has become widespread. It is, therefore, imperative to find compounds that could replace chloroquine or work synergistically with this drug to overcome chloroquine resistance. We have examined the interaction between chloroquine, a 4-aminoquinoline, and a number of 8-aminoquinolines, including primaquine, a drug that is widely used to treat Plasmodium vivax infections. We find that primaquine is a potent synergiser of the activity of chloroquine against chloroquine-resistant Plastnodium falciparum. Analysis of matched transfectants expressing mutant and wild-type alleles of the P.falciparum chloroquine resistance transporter (PfCRT) indicate that primaquine exerts its activity by blocking PfCRT, and thus enhancing chloroquine accumulation. Our data suggest that a novel formulation of two antimalarial drugs already licensed for use in humans could be used to treat chloroquine-resistant parasites. (c) 2005 Elsevier Inc. All rights reserved.