Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4611-3. doi: 10.1016/j.bmcl.2010.06.007. Epub 2010 Jun 8.

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.

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors*
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Cyclohexanones / chemistry*
  • Dimerization
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Mice
  • Oximes / chemical synthesis
  • Oximes / chemistry*
  • Oximes / pharmacology
  • Plasmodium berghei / drug effects
  • Triticum / enzymology*

Substances

  • Antimalarials
  • Cyclohexanones
  • Enzyme Inhibitors
  • Oximes
  • 1,3-cyclohexanedione
  • Acetyl-CoA Carboxylase