Abstract
This work is focused on the design of new antimicrobial drugs and on the development of lipophilic inhibitors of the DXR, the second enzyme of the MEP pathway for the biosynthesis of isoprene units in most bacteria, by replacing the phosphonate group of fosmidomycin derivatives by a tetrazoyl moiety capable of multiple hydrogen bonding. The N- and C-substituted tetrazole analogues of phosphonohydroxamate inhibitors were synthesized and tested on the DXR of Escherichia coli. This work points out the hypothesis that the phosphonate/phosphate recognition site might be too rigid to accommodate other functional groups.
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MeSH terms
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / metabolism
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Catalytic Domain
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Escherichia coli / metabolism
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Escherichia coli Proteins / antagonists & inhibitors
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Escherichia coli Proteins / metabolism
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Fosfomycin / analogs & derivatives
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Fosfomycin / chemistry
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Fosfomycin / metabolism
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Hydrogen Bonding
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / metabolism
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Multienzyme Complexes / antagonists & inhibitors*
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Multienzyme Complexes / metabolism
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Protein Binding
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Tetrazoles / chemical synthesis
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Tetrazoles / chemistry*
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Tetrazoles / metabolism
Substances
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Anti-Infective Agents
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Escherichia coli Proteins
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Hydroxamic Acids
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Multienzyme Complexes
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Tetrazoles
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1H-tetrazole
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Fosfomycin
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fosmidomycin