title: In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model.
abstract: 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 ED50 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.
authors: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India. drishti.agarwal17@gmail.com.|Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India. drishti.agarwal17@gmail.com.
authors: Drishti
authors: D
authors: Agarwal
authors: Department of Zoology, University of Delhi, Delhi, 110007, India. manish24jan@yahoo.com.
authors: Manish
authors: M
authors: Sharma
authors: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India. sandeepdixit99@gmail.com.
authors: Sandeep K
authors: SK
authors: Dixit
authors: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India. duttaroshan@gmail.com.
authors: Roshan K
authors: RK
authors: Dutta
authors: Department of Zoology, University of Delhi, Delhi, 110007, India. singhak.du@gmail.com.
authors: Ashok K
authors: AK
authors: Singh
authors: Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India. rdgupta@sau.ac.in.
authors: Rinkoo D
authors: RD
authors: Gupta
authors: Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India. satishpna@gmail.com.
authors: Satish K
authors: SK
authors: Awasthi
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004912:Erythrocytes / Q000469:parasitology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D024841:Fluoroquinolones; C031327:artemisinin
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