Abstract
Two series of FR900098/fosmidomycin analogs were synthesized and evaluated for MtDXR inhibition and Mycobacterium tuberculosis whole-cell activity. The design rationale of these compounds involved the exchange of either the phosphonic acid or the hydroxamic acid part for alternative acidic and metal-coordinating functionalities. The best inhibitors provided IC(50) values in the micromolar range, with a best value of 41 μM.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Aldose-Ketose Isomerases / antagonists & inhibitors*
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Aldose-Ketose Isomerases / metabolism
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Antitubercular Agents / chemical synthesis
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology*
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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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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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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Hydroxamic Acids / chemistry
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Multienzyme Complexes / antagonists & inhibitors*
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Multienzyme Complexes / metabolism
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / enzymology
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Organophosphonates / chemistry
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Oxidoreductases / antagonists & inhibitors*
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Oxidoreductases / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antitubercular Agents
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Enzyme Inhibitors
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Hydroxamic Acids
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Multienzyme Complexes
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Organophosphonates
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Fosfomycin
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fosmidomycin
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3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid
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Oxidoreductases
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1-deoxy-D-xylulose 5-phosphate reductoisomerase
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Aldose-Ketose Isomerases