Abstract
BackgroundEmergence 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).MethodsFluoroquinolone 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.ResultsPromising 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).ConclusionsIn vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.
Highlights
Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria
The results show that two out of the three compounds (10 and 18) exhibited appreciable antiplasmodial activity, reflected by their Median effective dose (ED50) values, comparable to that of the standard drug, artemisinin
Substantial evidence has been furnished that the fluoroquinolone analogues under assessment show inhibitory activities against the blood stages of the malaria parasite, with ED50 values in single-digit, micro-molar range
Summary
Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. A long time after its discovery back in the 1940s, other fluoroquinolones, such as norfloxacin, ciprofloxacin, pefloxacin, grepafloxacin, trovafloxacin, enoxacin, and clinofloxacin were evaluated against the malaria parasite in vitro [9,15,16] and in vivo [17,18,19] These common antibiotics were found efficacious against both chloroquine-sensitive and -resistant parasites, highly effective concentrations and prolonged treatment regimen (14 days) have restricted their use as sole therapy. These findings support further screening of newer fluoroquinolone compounds as partner drugs
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