title: Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax.
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 [IC(50)s], 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.
authors: Menzies School of Health Research, P.O. Box 41096, Casuarina, NT 0811, Darwin, Australia. Jutta.Marfurt@menzies.edu.au
authors: Jutta
authors: J
authors: Marfurt
authors: Ferryanto
authors: F
authors: Chalfein
authors: Pak
authors: P
authors: Prayoga
authors: Frans
authors: F
authors: Wabiser
authors: Enny
authors: E
authors: Kenangalem
authors: Kim A
authors: KA
authors: Piera
authors: Barbara
authors: B
authors: Machunter
authors: Emiliana
authors: E
authors: Tjitra
authors: Nicholas M
authors: NM
authors: Anstey
authors: Ric N
authors: RN
authors: Price
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D005296:Ferrous Compounds / Q000494:pharmacology*; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D002738:Chloroquine; C479230:ferroquine