Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity.
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.
Louie
Theola
T
The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia.
Goodman
C Dean
CD
Holloway
Georgina A
GA
McFadden
Geoffrey I
GI
Mollard
Vanessa
V
Watson
Keith G
KG
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*
D000962:Antimalarials; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D010091:Oximes; C004636:1,3-cyclohexanedione; D000103:Acetyl-CoA Carboxylase