title: Novel potent metallocenes against liver stage malaria.
abstract: Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ~45-fold-higher level activity against liver stage parasitemia than that of primaquine.
authors.affiliation: CIQUP-Centro de Investigação em Química da Universidade do Porto, Departamento de Químicae Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Matos
authors.forename: Filipa P
authors.initials: FP
authors.lastname: da Cruz
authors.forename: Élia
authors.initials: É
authors.lastname: Cabrita
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Fátima
authors.initials: F
authors.lastname: Nogueira
authors.forename: Virgílio E
authors.initials: VE
authors.lastname: do Rosário
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.forename: Paula
authors.initials: P
authors.lastname: Gomes
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects* / Q000469:parasitology; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission; D000075163:Metallocenes; D051379:Mice; D008807:Mice, Inbred BALB C; D033661:Oocysts / Q000187:drug effects / Q000502:physiology; D010962:Plasmodium berghei / Q000187:drug effects* / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D011319:Primaquine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D034101:Sporozoites / Q000187:drug effects / Q000502:physiology
chemical_list: D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D049452:Green Fluorescent Proteins; D011319:Primaquine; C004998:ferrocene