Abstract
The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel class of elongation condensing enzyme (FabB and FabF) inhibitors using a two-step virtual screening approach. Structure activity relationships were developed around the benzoxazolinone scaffold showing that N-substituted benzoxazolinones were most active. The benzoxazolinone scaffold has high chemical tractability making this chemotype suitable for further development of bacterial fatty acid synthesis inhibitors.
Keywords:
Antibiotics; Condensing enzymes; Fatty acid synthesis; Virtual screening.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / antagonists & inhibitors*
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / metabolism
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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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Benzoxazoles / chemical synthesis
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacology*
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical*
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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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Escherichia coli / drug effects*
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / metabolism
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Fatty Acid Synthase, Type II / antagonists & inhibitors*
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Fatty Acid Synthase, Type II / metabolism
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Benzoxazoles
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Enzyme Inhibitors
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Escherichia coli Proteins
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
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FabB protein, E coli
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Fatty Acid Synthase, Type II