Volume 85, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Ferroquine (FQ), a chloroquine (CQ) analog, is being developed to treat persons with malaria. In 146 field isolates from western Kenya, we measured 50% inhibitory concentrations (IC; nM) of CQ and FQ by a SYBR Green I assay. Reference clones included W2 (CQ resistant) and D6 (CQ sensitive). Mutation analysis was done for CQ-resistance transporter gene ( K76T). Median IC values for FQ were lower than CQ for field isolates and the W2 clone (both < 0.05). The mutation (76T), which was detected in > 80% of isolates, conferred higher CQ IC values ( < 0.05) and modestly lower FQ IC values ( < 0.05), versus wild type (K76). FQ is more potent than CQ against CQ-resistant field isolates and the W2 clone, and is less affected by 76T. These findings support the notion that FQ could be useful in treating persons with malaria.


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  1. Leimanis ML, Jaidee A, Sriprawat K, Kaewpongsri S, Suwanarusk R, Barends M, Phyo AP, Russell B, Renia L, Nosten F, , 2010. Plasmodium vivax susceptibility to ferroquine. Antimicrob Agents Chemother 54: 22282230.[Crossref] [Google Scholar]
  2. Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, Lebibi J, Deloron P, , 2003. In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooue region of Gabon. J Antimicrob Chemother 51: 10211024.[Crossref] [Google Scholar]
  3. Barends M, Jaidee A, Khaohirun N, Singhasivanon P, Nosten F, , 2007. In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border. Malar J 6: 81.[Crossref] [Google Scholar]
  4. Biot C, Taramelli D, Forfar-Bares I, Maciejewski LA, Boyce M, Nowogrocki G, Brocard JS, Basilico N, Olliaro P, Egan TJ, , 2005. Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity. Mol Pharm 2: 185193.[Crossref] [Google Scholar]
  5. Daher W, Biot C, Fandeur T, Jouin H, Pelinski L, Viscogliosi E, Fraisse L, Pradines B, Brocard J, Khalife J, Dive D, , 2006. Assessment of Plasmodium falciparum resistance to ferroquine (SSR97193) in field isolates and in W2 strain under pressure. Malar J 5: 11.[Crossref] [Google Scholar]
  6. Dubar F, Khalife J, Brocard J, Dive D, Biot C, , 2008. Ferroquine, an ingenious antimalarial drug: thoughts on the mechanism of action. Molecules 13: 29002907.[Crossref] [Google Scholar]
  7. Henry M, Briolant S, Fontaine A, Mosnier J, Baret E, Amalvict R, Fusai T, Fraisse L, Rogier C, Pradines B, , 2008. In vitro activity of ferroquine is independent of polymorphisms in transport protein genes implicated in quinoline resistance in Plasmodium falciparum . Antimicrob Agents Chemother 52: 27552759.[Crossref] [Google Scholar]
  8. Kreidenweiss A, Kremsner PG, Dietz K, Mordmuller B, , 2006. In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum . Am J Trop Med Hyg 75: 11781181. [Google Scholar]
  9. Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-Franco JG, Mollinedo RE, Avila JC, Cespedes JL, Carter D, Doumbo OK, , 1997. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176: 15901596.[Crossref] [Google Scholar]
  10. Mbaisi A, Liyala P, Eyase F, Achilla R, Akala H, Wangui J, Mwangi J, Osuna F, Alam U, Smoak BL, Davis JM, Kyle DE, Coldren RL, Mason C, Waters NC, , 2004. Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother 48: 35983601.[Crossref] [Google Scholar]
  11. Mwai L, Ochong E, Abdirahman A, Kiara SM, Ward S, Kokwaro G, Sasi P, Marsh K, Borrmann S, Mackinnon M, Nzila A, , 2009. Chloroquine resistance before and after its withdrawal in Kenya. Malar J 8: 106.[Crossref] [Google Scholar]
  12. Malakooti MA, Biomndo K, Shanks GD, , 1998. Reemergence of epidemic malaria in the highlands of western Kenya. Emerg Infect Dis 4: 671676.[Crossref] [Google Scholar]
  13. Bacon DJ, Latour C, Lucas C, Colina O, Ringwald P, Picot S, , 2007. Comparison of a SYBR green I-based assay with a histidine-rich protein II enzyme-linked immunosorbent assay for in vitro antimalarial drug efficacy testing and application to clinical isolates. Antimicrob Agents Chemother 51: 11721178.[Crossref] [Google Scholar]
  14. Johnson JD, Dennull RA, Gerena L, Lopez-Sanchez M, Roncal NE, Waters NC, , 2007. Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening. Antimicrob Agents Chemother 51: 19261933.[Crossref] [Google Scholar]
  15. Smilkstein M, Sriwilaijaroen N, Kelly JX, Wilairat P, Riscoe M, , 2004. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob Agents Chemother 48: 18031806.[Crossref] [Google Scholar]
  16. Akala HM, Eyase FL, Cheruiyot AR, Omondi AA, Ogutu BR, Waters NC, Johnson JD, Polhemus ME, Schnabel DC, Walsh DS, , 2011. Anti-malarial drug sensitivity profile of western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay, and molecular analysis. Am J Trop Med Hyg 85: 3441.[Crossref] [Google Scholar]
  17. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD, , 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16: 710718.[Crossref] [Google Scholar]
  18. Ferreira ID, Rosario VE, Cravo PV, , 2006. Real-time quantitative PCR with SYBR Green I detection for estimating copy numbers of nine drug resistance candidate genes in Plasmodium falciparum . Malar J 5: 1.[Crossref] [Google Scholar]
  19. Nelson AL, Purfield A, McDaniel P, Uthaimongkol N, Buathong N, Sriwichai S, Miller RS, Wongsrichanalai C, Meshnick SR, , 2005. pfmdr1 genotyping and in vivo mefloquine resistance on the Thai-Myanmar border. Am J Trop Med Hyg 72: 586592. [Google Scholar]
  20. Purfield A, Nelson A, Laoboonchai A, Congpuong K, McDaniel P, Miller RS, Welch K, Wongsrichanalai C, Meshnick SR, , 2004. A new method for detection of pfmdr1 mutations in Plasmodium falciparum DNA using real-time PCR. Malar J 3: 9.[Crossref] [Google Scholar]
  21. Blackie MA, Chibale K, Beagley P, Croft SL, Kendrick H, Moss JR, , 2008. Metallocene antimalarials: the continuing quest Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum . Met Based Drugs 2008: 495123.[Crossref] [Google Scholar]
  22. Delhaes L, Abessolo H, Biot C, Berry L, Delcourt P, Maciejewski L, Brocard J, Camus D, Dive D, , 2001. In vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl analogue of chloroquine against chloroquine-resistant malaria parasites. Parasitol Res 87: 239244.[Crossref] [Google Scholar]
  23. Delhaes L, Biot C, Berry L, Delcourt P, Maciejewski LA, Camus D, Brocard JS, Dive D, , 2002. Synthesis of ferroquine enantiomers: first investigation of effects of metallocenic chirality upon antimalarial activity and cytotoxicity. ChemBioChem 3: 418423.[Crossref] [Google Scholar]
  24. Mookherjee S, Howard V, Nzila-Mouanda A, Watkins W, Sibley CH, , 1999. Identification and analysis of dihydrofolate reductase alleles from Plasmodium falciparum present at low frequency in polyclonal patient samples. Am J Trop Med Hyg 61: 131140. [Google Scholar]
  25. Domarle O, Blampain G, Agnaniet H, Nzadiyabi T, Lebibi J, Brocard J, Maciejewski L, Biot C, Georges AJ, Millet P, , 1998. In vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine. Antimicrob Agents Chemother 42: 540544. [Google Scholar]
  26. Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, , 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209218.[Crossref] [Google Scholar]
  27. Holmgren G, Bjorkman A, Gil JP, , 2006. Amodiaquine resistance is not related to rare findings of pfmdr1 gene amplifications in Kenya. Trop Med Int Health 11: 18081812.[Crossref] [Google Scholar]
  28. Nkhoma S, Nair S, Mukaka M, Molyneux ME, Ward SA, Anderson TJ, , 2009. Parasites bearing a single copy of the multi-drug resistance gene (pfmdr-1) with wild-type SNPs predominate amongst Plasmodium falciparum isolates from Malawi. Acta Trop 111: 7881.[Crossref] [Google Scholar]

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  • Received : 24 Apr 2011
  • Accepted : 12 Sep 2011
  • Published online : 01 Dec 2011

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