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Ex Vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax

Marfurt, Jutta, Chalfein, Ferryanto, Prayoga, Pak, Wabiser, Frans, Kenangalem, Enny, Piera, Kim A., MacHunter, Barbara, Tjitra, Emiliana, Anstey, Nicholas M. and Price, Ric N. (2011). Ex Vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax. Antimicrobial Agents and Chemotherapy,55(9):4461-4464.

Document type: Journal Article
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Title Ex Vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax
Author Marfurt, Jutta
Chalfein, Ferryanto
Prayoga, Pak
Wabiser, Frans
Kenangalem, Enny
Piera, Kim A.
MacHunter, Barbara
Tjitra, Emiliana
Anstey, Nicholas M.
Price, Ric N.
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2011
Volume Number 55
Issue Number 9
ISSN 0066-4804   (check CDU catalogue  open catalogue search in new window)
Start Page 4461
End Page 4464
Total Pages 4
Place of Publication Washington, Unites States of America
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DIISR)
Abstract Ferroquine (FQ; SSR97193), a ferrocene-containing 4-aminoquinoline derivate, has potent in vitro efficacy against chloroquine (CQ)-resistant Plasmodium falciparum and CQ-sensitive P. vivax. In the current study, ex vivo FQ activity was tested in multidrug-resistant P. falciparum and P. vivax field isolates using a schizont maturation assay. Although FQ showed excellent activity against CQ-sensitive and -resistant P. falciparum and P. vivax (median 50% inhibitory concentrations [IC50s], 9.6 nM and 18.8 nM, respectively), there was significant cross-susceptibility with the quinoline-based drugs chloroquine, amodiaquine, and piperaquine (for P. falciparum, r = 0.546 to 0.700, P < 0.001; for P. vivax, r = 0.677 to 0.821, P < 0.001). The observed ex vivo cross-susceptibility is likely to reflect similar mechanisms of drug uptake/efflux and modes of drug action of this drug class. However, the potent activity of FQ against resistant isolates of both P. falciparum and P. vivax highlights a promising role for FQ as a lead antimalarial against CQ-resistant Plasmodium and a useful partner drug for artemisinin-based combination therapy.

DOI http://dx.doi.org/10.1128/AAC.01375-10   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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