title: In vitro efficiency of 9-(N-cinnamoylbutyl)aminoacridines against blood- and liver-stage malaria parasites.
abstract: Novel 9-aminoacridine derivatives were synthesized by linking the heteroaromatic core to different cinnamic acids through an aminobutyl chain. The test compounds demonstrated mid-nanomolar in vitro activity against erythrocytic stages of the chloroquine-resistant W2 strain of the human malaria parasite Plasmodium falciparum. Two of the most active derivatives also showed in vitro activity against liver-stage Plasmodium berghei, with activity greater than that of the reference liver-stage antimalarial primaquine. The compounds were not toxic to human hepatoma cells at concentrations up to 5 μM. Hence, 9-(N-cinnamoylbutyl)aminoacridines are a new class of leads for prevention and treatment of malaria.
authors.affiliation: Centro de Investigação em Química da Universidade do Porto, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, R. do Campo Alegre, 687, P-4169-007 Porto, Portugal.
authors.forename: Bianca
authors.initials: B
authors.lastname: Pérez
authors.forename: Cátia
authors.initials: C
authors.lastname: Teixeira
authors.forename: Ana S
authors.initials: AS
authors.lastname: Gomes
authors.forename: Inês S
authors.initials: IS
authors.lastname: Albuquerque
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
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: D000609:Aminoacridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D015394:Molecular Structure; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000609:Aminoacridines; D000962:Antimalarials; D002934:Cinnamates; C037551:cinnamoyl chloride