title: Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds.
abstract: A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodium falciparum. The quinoline compounds show enhanced activity compared to the ferrocene compounds against this parasite. Compound 5 displays the most promising activity against the NF54 strain. Compounds 5 and 6 are effective at inhibiting β-hematin formation perhaps due to an increased number of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds also inhibit β-hematin formation, albeit to a lesser degree compared to the quinoline thioureas. The compounds were also screened against the G3 strain of Trichomonas vaginalis and here the ferrocene-containing compounds show a slightly higher parasite growth inhibition compared to the quinoline thioureas. The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Tameryn
authors.initials: T
authors.lastname: Stringer
authors.forename: Dale
authors.initials: D
authors.lastname: Taylor
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.forename: Hajira
authors.initials: H
authors.lastname: Guzgay
authors.forename: Aaron
authors.initials: A
authors.lastname: Au
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: An
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sanchez
authors.forename: Raquel
authors.initials: R
authors.lastname: O'Connor
authors.forename: Neal
authors.initials: N
authors.lastname: Patel
authors.forename: Kirkwood M
authors.initials: KM
authors.lastname: Land
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Denver T
authors.initials: DT
authors.lastname: Hendricks
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Egan
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Smith
mesh_terms: D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011073:Polyamines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000977:Antiparasitic Agents; D003603:Cytotoxins; D011073:Polyamines; D013890:Thiourea
keywords: Antiparasitic activity; Antitumor activity; Ferrocene; Polyamines; Quinoline; Thioureas; β-Hematin inhibition