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<jats:title>ABSTRACT</jats:title><jats:p>Ferroquine (FQ; SSR97193), a ferrocene-containing 4-aminoquinoline derivate, has potent<jats:italic>in vitro</jats:italic>efficacy against chloroquine (CQ)-resistant<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium falciparum</jats:named-content>and CQ-sensitive<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>. In the current study,<jats:italic>ex vivo</jats:italic>FQ activity was tested in multidrug-resistant<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>field isolates using a schizont maturation assay. Although FQ showed excellent activity against CQ-sensitive and -resistant<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>(median 50% inhibitory concentrations [IC<jats:sub>50</jats:sub>s], 9.6 nM and 18.8 nM, respectively), there was significant cross-susceptibility with the quinoline-based drugs chloroquine, amodiaquine, and piperaquine (for<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>,<jats:italic>r</jats:italic>= 0.546 to 0.700,<jats:italic>P</jats:italic>&lt; 0.001; for<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>,<jats:italic>r</jats:italic>= 0.677 to 0.821,<jats:italic>P</jats:italic>&lt; 0.001). The observed<jats:italic>ex vivo</jats:italic>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<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>highlights a promising role for FQ as a lead antimalarial against CQ-resistant<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium</jats:named-content>and a useful partner drug for artemisinin-based combination therapy.</jats:p>

Original publication

DOI

10.1128/aac.01375-10

Type

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

09/2011

Volume

55

Pages

4461 - 4464