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

The in vitro activities of ferrochloroquine, chloroquine, quinine, mefloqui ne, halofantrine, amodiaquine, primaquine, atovaquone and artesunate were e valuated against Plasmodium faiciparum isolates from children with uncompli cated malaria from Libreville (Gabon), using an isotopic, micro, drug susce ptibility 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% Cl 8.6-13.5 nM), while the geometric means for chloroquine, quinine, mefloq uine, amodiaquine and primaquine were 370 nM, 341 nM, 8.3 nM, 18.1 nM and 7 .6 muM, respectively. Ferrochloroquine was active against P. faiciparum iso lates, 95% of which showed in vitro resistance to chloroquine. Weak positiv e significant correlations were observed between the responses to ferrochlo roquine and that to chloroquine, amodiaquine and quinine, but too low to su ggest cross-resistance. There was no significant correlation between the re sponse to ferrochloroquine and those to mefloquine, halofantrine, primaquin e, atovaquone or artesunate. Ferrochloroquine may be an important alternati ve drug for the treatment of chloroquine-resistant malaria.