Abstract
Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Catalytic Domain
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Citrates / chemical synthesis
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Citrates / chemistry*
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Computer Simulation
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Crystallography, X-Ray
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Drug Discovery
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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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Isocitrates / chemical synthesis
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Isocitrates / chemistry*
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beta-Lactamase Inhibitors*
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beta-Lactamases / metabolism
Substances
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Anti-Bacterial Agents
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Citrates
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Enzyme Inhibitors
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Isocitrates
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beta-Lactamase Inhibitors
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beta-lactamase PSE-2
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beta-Lactamases