Abstract
Based on the prodrug concept as well as the combination of two different classes of antimalarial agents, we designed and synthesized two series of ferrocenic antimalarial dual molecules consisting of a ferroquine analogue conjugated with a glutathione reductase inhibitor (or a glutathione depletor) through a cleavable amide bond in order to target two essential pathways in the malarial parasites. The results showed no enhancement of the antimalarial activity of the dual molecules but evidenced a unique mode of action of ferroquine and ferrocenyl analogues distinct of those of chloroquine and nonferrocenic 4-aminoquinoline analogues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoquinolines / chemical synthesis*
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Aminoquinolines / chemistry
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Aminoquinolines / pharmacology
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Antimalarials / chemical synthesis*
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Antimalarials / chemistry
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Antimalarials / pharmacology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Ferrous Compounds / chemical synthesis*
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology
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Hemin / metabolism
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Humans
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Magnetic Resonance Spectroscopy
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Plasmodium falciparum / growth & development
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Spectrometry, Mass, Electrospray Ionization
Substances
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Aminoquinolines
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Antimalarials
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Enzyme Inhibitors
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Ferrous Compounds
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Prodrugs
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Hemin