Potent enhancement of the sensitivity of Plasmodium falciparum to chloroquine by the bisbenzylisoquinoline akaloid cepharanthin

被引:17
作者
Haruki, K
Bray, PG [1 ]
Ono, M
Ward, SA
机构
[1] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England
[2] Kaken Shoyaku Co Ltd, Res Labs, Tokyo 1810013, Japan
[3] Kyorin Univ Med, Dept Trop Dis & Parasitol, Mitaka, Tokyo 1818611, Japan
关键词
D O I
10.1128/AAC.44.10.2706-2708.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cepharanthin is a proprietary extract of Stephania cepharantha, widely used in Japan for the treatment of inflammatory diseases. Cephranthin, its component alkaloids, and the standard resistance modulator verapamil were tested against Plasmodium falciparum for capacity to modulate sensitivity to chloroquine. Cepharanthin enhanced the activity of chloroquine against resistant clones by a factor of 15 at a concentration of only 200 nM (1.2 ng/ml). It is 50 times more potent than verapamil and 3 times more potent than the sum of its individual alkaloids. Combinations of component alkaloids acted synergistically to sensitize the parasite to chloroquine, possibly explaining the enhanced potency of Cepharanthin. Cepharanthin differed from verapamil in that it further sensitized clones that are considered to he fully susceptible, improving the baseline activity of chloroquine. Potent sensitization of parasites to chloroquine in vitro coupled with low toxicity suggests that coadministration of Cepharanthin might extend the clinical utility of chloroquine.
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页码:2706 / 2708
页数:3
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