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 antimal arial activity against Plasmodium spp. The present work confirmed this acti vity, described the curative effect on P. vinckei and investigated the FQ t oxicity 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 inhib ited 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 curativ e effect was 5-20 times more potent than chloroquine, according to the stra ins' resistance to chloroquine. At this curative dose, no clinical changes were observed in mice up to 14 days after the last administration. Neverthe less, the acute toxicity and lethality of ferrochloroquine seemed to be dep endent on gastric surfeit, The FQ security index determined in vitro confir med that it might be a promising compound.