Novel short chain chloroquine analogues retain activity against chloroquine resistant K1 Plasmodium falciparum

被引:123
作者
Stocks, PA
Raynes, KJ
Bray, PG
Park, BK
O'Neill, PM
Ward, SA
机构
[1] Univ Liverpool, Dept Chem, Liverpool L69 3BX, Merseyside, England
[2] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England
关键词
D O I
10.1021/jm0108707
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of short chain chloroquine (CQ) derivatives have been synthesized in one step from readily available starting materials. The diethylamine function of CQ is replaced by shorter alkylamine groups (4-9) containing secondary or tertiary terminal nitrogens. Some of these derivatives are significantly more potent than CQ against a CQ resistant strain of Plasmodium falciparum in vitro. We conclude that the ability to accumulate at higher concentrations within the food vacuole of the parasite is an important parameter that dictates their potency against CQ sensitive and the chloroquine resistant K1 P. falciparum.
引用
收藏
页码:4975 / 4983
页数:9
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