Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum

• Published in: Journal of antimicrobial chemotherapy 2001-08, Vol.48 (2), p.179-184
• Main Authors: Pradines, B., Fusai, T., Daries, W., Laloge, V., Rogier, C., Millet, P., Panconi, E., Kombila, M., Parzy, D.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Child; Child, Preschool; Chloroquine - analogs & derivatives; Chloroquine - chemistry; Chloroquine - pharmacology; Drug Resistance; Ferrochloroquine; Ferrous Compounds - chemistry; Ferrous Compounds - pharmacology; Humans; In Vitro Techniques; Malaria, Falciparum - drug therapy; Medical sciences; Metallocenes; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - isolation & purification; Quinine
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/48.2.179

The in vitro activities of ferrochloroquine, chloroquine, quinine, mefloquine, halofantrine, amodiaquine, primaquine, atovaquone and artesunate were evaluated against Plasmodium falciparum isolates from children with uncomplicated malaria from Libreville (Gabon), using an isotopic, micro, drug susceptibility test. The IC50 values for ferrochloroquine were in the range 0.43–30.9 nM and the geometric mean IC50 for the 103 isolates was 10.8 nM (95% CI 8.6–13.5 nM), while the geometric means for chloroquine, quinine, mefloquine, amodiaquine and primaquine were 370 nM, 341 nM, 8.3 nM, 18.1 nM and 7.6 μM, respectively. Ferrochloroquine was active against P. falciparum isolates, 95% of which showed in vitro resistance to chloroquine. Weak positive significant correlations were observed between the responses to ferrochloroquine and that to chloroquine, amodiaquine and quinine, but too low to suggest cross-resistance. There was no significant correlation between the response to ferrochloroquine and those to mefloquine, halofantrine, primaquine, atovaquone or artesunate. Ferrochloroquine may be an important alternative drug for the treatment of chloroquine-resistant malaria.