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Exploring the trifluoromenadione core as a template to design antimalarial redox-active agents interacting with glutathione reductase

Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditi...

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Bibliographic Details
Main Authors: Lanfranchi, Don A. (Author) , Müller, Tobias (Author) , Lanzer, Michael (Author) , Davioud-Charvet, Elisabeth (Author)
Format: Article (Journal)
Language:English
Published: 17 Apr 2012
In: Organic & biomolecular chemistry
Year: 2012, Volume: 10, Issue: 24, Pages: 4795-4806
ISSN:1477-0539
DOI:10.1039/C2OB25229E
Online Access:Verlag, Volltext: http://dx.doi.org/10.1039/C2OB25229E
Verlag, Volltext: https://pubs.rsc.org/en/content/articlelanding/2012/ob/c2ob25229e
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Author Notes:Don Antoine Lanfranchi, Didier Belorgey, Tobias Müller, Hervé Vezin, Michael Lanzer, Elisabeth Davioud-Charvet
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Summary:Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions, is discussed in terms of chemical synthesis, electrochemistry, enzyme kinetics, and antimalarial activities. Multitarget-directed drug discovery is an emerging approach to the design of new antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial drug atovaquone, revealed a mechanism for CF3 as a leaving group. The resulting trifluoromethyl derivative 5 showed a potent antimalarial activity per se against malarial parasites in culture.
Item Description:Gesehen am 18.10.2018
Physical Description:Online Resource
ISSN:1477-0539
DOI:10.1039/C2OB25229E

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