title: Inhibitory activity of ferroquine, versus chloroquine, against western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay.
abstract: Ferroquine (FQ), a chloroquine (CQ) analog, is being developed to treat persons with Plasmodium falciparum malaria. In 146 P. falciparum field isolates from western Kenya, we measured 50% inhibitory concentrations (IC(50); nM) of CQ and FQ by a SYBR Green I in vitro assay. Reference clones included W2 (CQ resistant) and D6 (CQ sensitive). Mutation analysis was done for P. falciparum CQ-resistance transporter gene (Pfcrt K76T). Median IC(50) values for FQ were lower than CQ for field isolates and the W2 clone (both P < 0.05). The Pfcrt mutation (76T), which was detected in > 80% of isolates, conferred higher CQ IC(50) values (P < 0.05) and modestly lower FQ IC(50) values (P < 0.05), versus Pfcrt wild type (K76). FQ is more potent than CQ against CQ-resistant P. falciparum field isolates and the W2 clone, and is less affected by Pfcrt 76T. These findings support the notion that FQ could be useful in treating persons with P. falciparum malaria.
authors.affiliation: Department of Emerging Infectious Diseases Program, U.S. Army Medical Research Unit-Kenya, Kenya Medical Research Institute-Walter Reed Project, Kisumu, Kenya. feyase@wrp-ksm.org
authors.forename: Fredrick L
authors.initials: FL
authors.lastname: Eyase
authors.forename: Hoseah M
authors.initials: HM
authors.lastname: Akala
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Johnson
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Walsh
mesh_terms: D000634:Aminoquinolines / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005296:Ferrous Compounds / Q000627:therapeutic use*; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000188:drug therapy*; D026901:Membrane Transport Proteins / Q000235:genetics; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D026901:Membrane Transport Proteins; D000075163:Metallocenes; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine; C479230:ferroquine