title: Mono- and multimeric ferrocene congeners of quinoline-based polyamines as potential antiparasitics.
abstract: A series of mono- and multimeric polyamine-containing ferrocenyl complexes containing a quinoline motif were prepared. The complexes were characterised by standard techniques. The molecular structure of the monomeric salicylaldimine derivative was elucidated using single crystal X-ray diffraction and was consistent with the proposed structure. The antiplasmodial activity of the compounds were evaluated in vitro against both the NF54 (chloroquine-sensitive) and K1 (chloroquine-resistant) strains of Plasmodium falciparum. The polyamine derivatives exhibit good resistance index values suggesting that these systems are beneficial in overcoming the resistance experienced by chloroquine. Mechanistic studies suggest that haemozoin formation may be the target of these quinoline complexes in the parasite. Some of the complexes exhibit moderate to high cytotoxicity against WHCO1 oesophageal cancer cells in vitro. The monomeric ferrocenyl-amine complexes exhibit potent activity against this particular cell line. The complexes were also screened against the G3 strain of Trichomonas vaginalis and the salicylaldimine complexes demonstrated promising activity at the tested concentration. All of these compounds show no inhibitory effect on several common normal flora bacteria, indicative of their selectivity for eukaryotic pathogens and cancer.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa. Gregory.Smith@uct.ac.za.
authors.forename: Tameryn
authors.initials: T
authors.lastname: Stringer
authors.forename: Carmen
authors.initials: C
authors.lastname: De Kock
authors.forename: Hajira
authors.initials: H
authors.lastname: Guzgay
authors.forename: John
authors.initials: J
authors.lastname: Okombo
authors.forename: Jenny
authors.initials: J
authors.lastname: Liu
authors.forename: Sierra
authors.initials: S
authors.lastname: Kanetake
authors.forename: Jihwan
authors.initials: J
authors.lastname: Kim
authors.forename: Christina
authors.initials: C
authors.lastname: Tam
authors.forename: Luisa W
authors.initials: LW
authors.lastname: Cheng
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Denver T
authors.initials: DT
authors.lastname: Hendricks
authors.forename: Kirkwood M
authors.initials: KM
authors.lastname: Land
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Egan
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Smith
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004351:Drug Resistance; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes / Q000737:chemistry*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry*; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D000977:Antiparasitic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D011073:Polyamines; D011804:Quinolines; C037219:quinoline; C004998:ferrocene