Abstract
We describe the synthesis and antibacterial activity of a series of tetracyclic naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). In this paper we explore the structure-activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of <5 microM and have minimum inhibitory concentrations (MICs) of <8 microg/mL against clinically relevant strains of bacteria.
MeSH terms
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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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B-Lymphocytes / drug effects
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Drug Resistance, Bacterial
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Microbial Sensitivity Tests
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Naphthyridines / chemical synthesis*
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Naphthyridines / chemistry
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Naphthyridines / pharmacology
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Protein Biosynthesis / drug effects
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Stereoisomerism
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Streptococcus pneumoniae / drug effects
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Streptococcus pneumoniae / genetics
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Streptococcus pneumoniae / isolation & purification
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Heterocyclic Compounds, 4 or More Rings
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Naphthyridines