title: Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity.
abstract: A series of dimeric 1,3-cyclohexanedione oxime ethers were synthesized and found to have significant antiplasmodial activity with IC(50)'s in the range 3-12 microM. The most active dimer was tested in the Plasmodium berghei mouse model of malaria and at a dose of 48 mg/kg gave a 45% reduction in parasitaemia. Several commercial herbicides, all known to be inhibitors of maize acetyl-CoA carboxylase, were also tested for antimalarial activity, but were essentially inactive with the exception of butroxydim which gave an IC(50) of 10 microM.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia.
authors.forename: Theola
authors.initials: T
authors.lastname: Louie
authors.forename: C Dean
authors.initials: CD
authors.lastname: Goodman
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Holloway
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mollard
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003512:Cyclohexanones / Q000737:chemistry*; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects; D014908:Triticum / Q000201:enzymology*
chemical_list: D000962:Antimalarials; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D010091:Oximes; C004636:1,3-cyclohexanedione; D000103:Acetyl-CoA Carboxylase