Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity
Graphical abstract
A variety of acetyl-CoA carboxylase inhibitors were tested against malaria with butroxydim 5 and the dimeric 1,3-cyclohexanedione 11 showing activity in the Plasmodium berghei mouse model.
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Cited by (15)
Synthetic approaches for cyclohexane-1,3-diones: A versatile precursor for bioactive molecules
2021, Synthetic CommunicationsDrug targets in the apicoplast
2020, Antimalarial Agents: Design and Mechanism of ActionRelict plastidic metabolic process as a potential therapeutic target
2018, Drug Discovery TodayCitation Excerpt :The sequence features for apicoplast localization are confirmed by epitope tagging studies [76]. The herbicides like fops and dims were previously known to target ACC [23,63,77]; however, the elongase pathway for fatty acid extension is believed to be affected by them [78]. FabD (malonyl-CoA:ACP transacylase) catalyzes production of malonyl-ACP from malonyl-CoA.
Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts
2015, Molecular and Biochemical ParasitologyCitation Excerpt :In efforts to develop more potent inhibitors, a myriad of studies were then undertaken in both Plasmodium and T. gondii. Numerous compounds were tested for inhibition of parasite growth [41–61], and many FASII enzymes were characterized [49,52,55,62–79], allowing further optimization of lead compounds against their putative targets. These studies identified several promising anti-malarial drug candidates, some of which displayed activity against bloodstage parasites at nanomolar concentrations [54,59].
Apicoplast acetyl Co-A carboxylase of the human malaria parasite is not targeted by cyclohexanedione herbicides
2014, International Journal for ParasitologyCitation Excerpt :There was no observable difference in the growth response of the knockout parasites when compared with the parental strains. The observed IC50 values of the deletion parasites (Table 1) were in agreement with those reported previously (Louie et al., 2010) and there was no significant difference in the IC50 values found between the parasite lines carrying the gene deletion and wild type strains for either compound. Similar results were found for when the inhibitor dimeric cyclohexane-1,3-dione oxime 11 (Louie et al., 2010) was tested against the 3D7 and 3D7 KO2 parasite lines (Table 1) with no significant differences between the IC50 values for the two lines.