title: Chloroquine-astemizole hybrids with potent in vitro and in vivo antiplasmodial activity.
abstract: A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds 5-8 possessed improved in vitro activity against a CQ-resistant strain of Plasmodium falciparum, and examples 7 and 8 were active in vivo in mouse models of malaria.
authors.affiliation: Department of Chemistry, University of Cape Town, P/B Rondebosch 7700, Cape Town, South Africa.
authors.forename: Chitalu C
authors.initials: CC
authors.lastname: Musonda
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Whitlock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Witty
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D016589:Astemizole / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D016589:Astemizole; D002738:Chloroquine