title: A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum.
abstract: A class of hybrid molecules which we term 'reversed chloroquines' (RCQs) was designed, and a prototype molecule, N'-(7-chloroquinolin-4-yl)-N-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]-N-methylpropane-1,3-diamine (1), was synthesized and tested against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. An in vitro assay against the two strains indicated that 1 was effective at low-nM concentrations against both strains. A preliminary study in mice demonstrated oral efficacy against P. chabaudi and the absence of obvious toxicity. The RCQ approach therefore appears to be feasible.
authors.affiliation: Department of Chemistry, Portland State University, P.O. Box 751, Portland, Oregon 97207-0751, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burgess
authors.forename: Audrey
authors.initials: A
authors.lastname: Selzer
authors.forename: Jane Xu
authors.initials: JX
authors.lastname: Kelly
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Smilkstein
authors.forename: Michael K
authors.initials: MK
authors.lastname: Riscoe
authors.forename: David H
authors.initials: DH
authors.lastname: Peyton
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003984:Dibenzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D016788:Plasmodium chabaudi; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D003984:Dibenzazepines; C514071:N'-(7-chloroquinolin-4-yl)-N-(3-(10,11-dihydrodibenzo(b,f)azepin-5-yl)propyl)-N-methylpropane-1,3-diamine; D002738:Chloroquine