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Antimicrobial Agents and Chemotherapy, February 2005, p. 493-496, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.493-496.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Potent Plasmodicidal Activity of a Heat-Induced Reformulation of Deoxycholate-Amphotericin B (Fungizone) against Plasmodium falciparum

Gunma University School of Health Sciences,¹ Department of Parasitology, Gunma University School of Medicine, Showa-machi, Maebashi,² Research Institute, International Medical Center of Japan, Toyama, Shinjyuku-ku, Tokyo, Japan³

Received 29 June 2004/ Returned for modification 9 July 2004/ Accepted 6 October 2004

The emergence and spread of drug-resistant Plasmodium falciparum continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against P. falciparum was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 ± 0.03 µg/ml for strain K-1 and 0.33 ± 0.03 µg/ml for strain FCR-3. In the presence of 1.0 µg of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 µg of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.

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