In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model

Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their a...

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Bibliographic Details
Published in:Malaria journal 2015-02, Vol.14 (1), p.48, Article 48
Main Authors: Agarwal, Drishti, Sharma, Manish, Dixit, Sandeep K, Dutta, Roshan K, Singh, Ashok K, Gupta, Rinkoo D, Awasthi, Satish K
Format: Article
Language:English
Subjects:
Animals
Antimalarials - pharmacology
Artemisinins - pharmacology
Cells, Cultured
Control
Drug Synergism
Drug therapy
Drug therapy, Combination
Erythrocytes - parasitology
Fluoroquinolones - pharmacology
Health aspects
Humans
Malaria
Mice
Plasmodium berghei - drug effects
Plasmodium falciparum - drug effects
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Summary:Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their anti-malarial interaction in combination with artemisinin in vitro, against Plasmodium falciparum 3D7 strain, employing fixed-ratio combination isobologram method. In addition, the efficacy of these compounds was evaluated intraperitoneally in BALB/c mice infected with chloroquine-resistant Plasmodium berghei ANKA strain in the Peters' four-day suppressive test. Promising results were obtained in the form of synergistic or additive interactions. Compounds 10 and 12 were found to have highly synergistic interactions with artemisinin. Antiplasmodial effect was further verified by the convincing ED50 values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW). In vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.
ISSN:1475-2875
1475-2875
DOI:10.1186/s12936-015-0561-2