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, 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 IC(50) values for ferrochloroquine were in the range 0.43-30.9 nM and the geometric mean IC(50) 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 microM, 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.
Pradines
B
B
Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, Bd C. Livon, Parc Le Pharo, BP 46, 13998 Marseille Armées, France. bruno.pradines@free.fr
Fusai
T
T
Daries
W
W
Laloge
V
V
Rogier
C
C
Millet
P
P
Panconi
E
E
Kombila
M
M
Parzy
D
D
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000188:drug therapy; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification
D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D002738:Chloroquine; C004998:ferrocene