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Background  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).    Methods  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.    Results  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 ED 50  values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW).    Conclusions   In vivo  studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.

malaria journal

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