title: Synthesis and in vitro antiplasmodial activity of quinoline-ferrocene esters.
abstract: New 4-aminoquinoline-derived esters containing the redox-active ferrocene group brought in by either ferrocenyformic or 4-ferrocenylbutanoic acids were synthesized and tested in vitro for their antiplasmodial activity. The results revealed that only esters derived from ferrocenylformic acid were active against both chloroquine (CQ)-resistant Dd2 and CQ-sensitive D10 strains of Plasmodium falciparum. However, none of these showed higher actvity than CQ against the sensitive strain. Ester 16, which possesses a butyl branch in the structure, was the most active of all. With an IC50 of 0.13 mM on the resistant strain, this ester possessed 2.5-fold higher activity than CQ (IC50 = 0.34 mM). All tested esters showed good selectivity towards P. falciparum with indexes higher than 60.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa. david.nda@nwu.ac.za
authors.forename: David D
authors.initials: DD
authors.lastname: N'Da
authors.forename: Jaco C
authors.initials: JC
authors.lastname: Breytenbach
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Carmen
authors.initials: C
authors.lastname: Lategan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells; D002738:Chloroquine / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003412:Cricetulus; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005296:Ferrous Compounds; D007202:Indicators and Reagents; D000075163:Metallocenes; D011804:Quinolines; D002738:Chloroquine; C004998:ferrocene