Abstract
A series of fosmidomycin analogues featuring restricted conformational mobility has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and proved equally active when tested in vitro for P. falciparum growth inhibition. Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no inhibition of the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldose-Ketose Isomerases / antagonists & inhibitors
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Animals
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Fosfomycin / analogs & derivatives*
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Fosfomycin / chemical synthesis
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Fosfomycin / chemistry
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Fosfomycin / pharmacology
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In Vitro Techniques
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Molecular Structure
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Multienzyme Complexes / antagonists & inhibitors
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Oxidoreductases / antagonists & inhibitors
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Parasitic Sensitivity Tests
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Plasmodium falciparum / cytology
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / growth & development*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Multienzyme Complexes
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Fosfomycin
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fosmidomycin
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Oxidoreductases
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1-deoxy-D-xylulose 5-phosphate reductoisomerase
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Aldose-Ketose Isomerases