Bioorganic & Medicinal Chemistry Letters 2010-08-01

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

Theola Louie, C Dean Goodman, Georgina A Holloway, Geoffrey I McFadden, Vanessa Mollard, Keith G Watson

Index: Bioorg. Med. Chem. Lett. 20 , 4611-3, (2010)

Full Text: HTML

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.Copyright 2010 Elsevier Ltd. All rights reserved.