Synthesis and in vitro antiplasmodial activityof quinoline-ferrocene esters

Abstract

New 4-aminoquinoline-derived esterscontaining the redox-active ferrocenegroup brought in by either ferrocenyfor-mic or 4-ferrocenylbutanoic acids weresynthesized and tested in vitro for theirantiplasmodial activity. The results re-vealed that only esters derived from fer-rocenylformic acid were active againstboth chloroquine (CQ)-resistant Dd2 andCQ-sensitive D10 strains of Plasmodium falciparum. However, none of theseshowed higher actvity than CQ against the sensitive strain. Ester 16, which pos-sesses a butyl branch in the structure,was the most active of all. With an IC₅₀ of0.13 mM on the resistant strain, this esterpossessed 2.5-fold higher activity than CQ(IC₅₀ = 0.34 mM). All tested esters showedgood selectivity towards P. falciparum with indexes higher than 60.

Key words

Antiplasmodial activity - Chloroquine - Cytotoxicity - Ferrocene - Plasmodium falciparum

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