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Review
. 2011 Aug;18(3):207-14.
doi: 10.1051/parasite/2011183207.

The antimalarial ferroquine: from bench to clinic

C Biot  1 , F Nosten, L Fraisse, D Ter-Minassian, J Khalife, D Dive
Affiliations
Review

The antimalarial ferroquine: from bench to clinic

C Biot et al. Parasite. 2011 Aug.

Abstract
in English, French

Ferroquine (FQ, SSR97193) is currently the most advanced organo-metallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocene-containing compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.

La ferroquine (FQ, SSR97193) est actuellement le candidat médicament organométallique le plus avancé dans son développement industriel et, en tant que traitement du paludisme non compliqué, il devrait bientôt voir s’achever des études cliniques de phase II. Ce composé à base de ferrocène est extrêmement actif contre des isolats et/ou des clones de Plasmodium falciparum et de P. vivax sensibles ou résistants à la chloroquine. Cet article présente la découverte de la FQ, son activité antipaludique, les hypothèses liées à son mode d’action, l’absence actuelle de résistance in vitro et, enfin, les récents essais cliniques.

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Figures

Fig 1.
Fig 1.
Scheme of different strategies adopted in synthesis of ferrocene-CQ hybrids.
Fig 2.
Fig 2.
Susceptibility of 19 laboratory P. falciparum clones to CQ and FQ compiled from 11 different published studies. IC50 for CQ for each clone tested (l). + IC50 for FQ for each clone tested (+). The doted line indicate the threshold of resistance to CQ (Le Bras & Ringwald, 1990). References associated to each clone tested: 3D7 (1, 6, 8, 9, 10); HB3 (1, 7, 9, 10); D10 (2, 3, 4, 5); W2 (1, 6, 8, 9, 10); K1 (2, 3, 4, 5); FCR3 (1, 6, 11); Dd2 (7, 10, 11); D6, 106/1, IMT8425, IMT10336, FCM39, IMT Bres, IMT K14, IMT K2, IMT K4, IMT L1, IMT Vol, Bre1 (1). References: 1: Henry et al., 2008; 2: Beagley et al., 2002; 3: Beagley et al., 2003, 4: Blackie et al., 2007; 5: Blackie & Chibale 2008; 6 Biot et al., 2006b; 7: Biot et al., 1999; 8: Biot et al., 2006a; 9: Daher, et al., 2006a; 10: Daher, et al., 2006b; 11: Delhaes et al., 2001.
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