In vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl analogue of chloroquine against chloroquine-resistant malaria parasites.
Previous studies have shown that ferrochloroquine (FQ) exhibited an antimalarial activity against Plasmodium spp. The present work confirmed this activity, described the curative effect on P. vinckei and investigated the FQ toxicity in vitro and in vivo. The in vitro and in vivo growth inhibition of P. falciparum and P. berghei N, respectively, showed that FQ antimalarial activity was 1.5-10 times more potent than chloroquine. FQ completely inhibited the in vivo development of both chloroquine-susceptible and resistant P. vinckei strains and protected mice from lethal infection at a dose of 8.4 mg kg(-1) day(-1) given for 4 days subcutaneously or orally. This curative effect was 5-20 times more potent than chloroquine, according to the strains' resistance to chloroquine. At this curative dose, no clinical changes were observed in mice up to 14 days after the last administration. Nevertheless, the acute toxicity and lethality of ferrochloroquine seemed to be dependent on gastric surfeit. The FQ security index determined in vitro confirmed that it might be a promising compound.
Delhaes
L
L
INSERM Unité 167, Institut Pasteur, Lille, France.
Abessolo
H
H
Biot
C
C
Berry
L
L
Delcourt
P
P
Maciejewski
L
L
Brocard
J
J
Camus
D
D
Dive
D
D
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D005296:Ferrous Compounds; D007279:Injections, Subcutaneous; D008223:Lymphoma; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000662:veterinary*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D012376:Rodent Diseases / Q000517:prevention & control*
D000962:Antimalarials; D005296:Ferrous Compounds; D002738:Chloroquine