Abstract
Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent.
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / biosynthesis*
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Gram-Negative Bacteria / drug effects
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Gram-Negative Bacteria / growth & development
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Gram-Positive Bacteria / drug effects
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Gram-Positive Bacteria / growth & development
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Microbial Sensitivity Tests
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Naphthyridines / chemistry*
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Naphthyridines / pharmacology
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Protein Synthesis Inhibitors / chemistry*
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Protein Synthesis Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Naphthyridines
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Protein Synthesis Inhibitors