title: Synthesis, antimalarial activity and inhibition of haem detoxification of novel bisquinolines.
abstract: The synthesis of novel bisquinoline compounds comprising 4-(4-diethylamino-1-methylbutyl)aminoquinoline units joined through the 2-position by a (CH(2))(n) linker is described. Their ability to inhibit the growth of both chloroquine-sensitive (D10) and chloroquine-resistant (K1) strains of Plasmodium falciparum, the hydrogen peroxide-mediated pathway for decomposition of haem, and the conversion of haem to beta-haematin have been measured. The activity was affected by the length of the linker and the most active (6c, n=12) showed effects similar to chloroquine in three of the assays. However, it was even more active against the resistant strain [IC(50), 17 nM (K1); 43 nM (D10)], much superior to chloroquine (IC(50), 540 nM) and slightly better than mefloquine (IC(50), 30 nM) in this regard.
authors.affiliation: Department of Chemistry, La Trobe University, 3086, Victoria, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Ayad
authors.forename: L
authors.initials: L
authors.lastname: Tilley
authors.forename: L W
authors.initials: LW
authors.lastname: Deady
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D008658:Inactivation, Metabolic; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D011804:Quinolines; D002738:Chloroquine