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Antimicrobial Agents and Chemotherapy, October 2000, p. 2706-2708, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Potent Enhancement of the Sensitivity of Plasmodium falciparum to Chloroquine by the Bisbenzylisoquinoline Alkaloid Cepharanthin

Kosuke Haruki,1 Patrick G. Bray,2,* Minoru Ono,3 and Stephen A. Ward2

Department of Tropical Diseases and Parasitology, Kyorin University of Medicine, Mitaka, 181-8611 Tokyo,1 and Research Laboratories, Kaken Shoyaku Co., Ltd., Mitaka, 181-0013 Tokyo,3 Japan, and Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool L69 3BX, United Kingdom2

Received 17 April 2000/Returned for modification 7 June 2000/Accepted 5 July 2000

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 be 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.

* Corresponding author. Mailing address: Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool L69 3BX, United Kingdom. Phone: 44-151-794-8218. Fax: 44-151-794-8217. E-mail: p.g.bray{at}liv.ac.uk.

Antimicrobial Agents and Chemotherapy, October 2000, p. 2706-2708, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

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  • van Schalkwyk, D. A., Walden, J. C., Smith, P. J. (2001). Reversal of Chloroquine Resistance in Plasmodium falciparum Using Combinations of Chemosensitizers. Antimicrob. Agents Chemother. 45: 3171-3174 [Abstract] [Full Text]  


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