Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum

Toshimitsu Hatabu, Tsuyoshi Takada, Nao Taguchi, Mamoru Suzuki, Kumiko Sato, Shigeyuki Kano

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)493-496
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number2
DOIs
Publication statusPublished - Feb 2005
Externally publishedYes

Fingerprint

Amphotericin B
Plasmodium falciparum
Hot Temperature
Trophozoites
Schizonts
Chloroquine
deoxycholate drug combination amphotericin B
Erythrocyte Count
Falciparum Malaria
Liver
Antimalarials
Pharmaceutical Preparations
Inhibitory Concentration 50
Malaria
Parasites
Drug Therapy
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum. / Hatabu, Toshimitsu; Takada, Tsuyoshi; Taguchi, Nao; Suzuki, Mamoru; Sato, Kumiko; Kano, Shigeyuki.

In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 2, 02.2005, p. 493-496.

Research output: Contribution to journalArticle

Hatabu, Toshimitsu ; Takada, Tsuyoshi ; Taguchi, Nao ; Suzuki, Mamoru ; Sato, Kumiko ; Kano, Shigeyuki. / Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum. In: Antimicrobial Agents and Chemotherapy. 2005 ; Vol. 49, No. 2. pp. 493-496.
@article{3018fc2f73854a999747d2e893d21240,
title = "Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum",
abstract = "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.",
author = "Toshimitsu Hatabu and Tsuyoshi Takada and Nao Taguchi and Mamoru Suzuki and Kumiko Sato and Shigeyuki Kano",
year = "2005",
month = "2",
doi = "10.1128/AAC.49.2.493-496.2005",
language = "English",
volume = "49",
pages = "493--496",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum

AU - Hatabu, Toshimitsu

AU - Takada, Tsuyoshi

AU - Taguchi, Nao

AU - Suzuki, Mamoru

AU - Sato, Kumiko

AU - Kano, Shigeyuki

PY - 2005/2

Y1 - 2005/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=12944305792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12944305792&partnerID=8YFLogxK

U2 - 10.1128/AAC.49.2.493-496.2005

DO - 10.1128/AAC.49.2.493-496.2005

M3 - Article

C2 - 15673723

AN - SCOPUS:12944305792

VL - 49

SP - 493

EP - 496

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 2

ER -