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

J Marfurt, Ferryanto Chalfein, P Prayoga, Frans Wabiser, E Kenangalem, Kim Piera, B MacHunter, E Tjitra, Nicholas Anstey, Ric Price

    Research output: Contribution to journalArticlepeer-review

    36 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)4461-4464
    Number of pages4
    JournalAntimicrobial Agents and Chemotherapy
    Volume55
    Issue number9
    DOIs
    Publication statusPublished - Sept 2011

    Fingerprint

    Dive into the research topics of 'Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax'. Together they form a unique fingerprint.

    Cite this