Abstract
SB-203207 and 10 analogues have been prepared, by elaboration of altemicidin, and evaluated as inhibitors of isoleucyl, leucyl and valyl tRNA synthetases (IRS, LRS, and VRS, respectively). Substituting the isoleucine residue of SB-203207 with leucine and valine increased the potency of inhibition of LRS and VRS, respectively. The leucine derivative showed low level antibacterial activity, while several of the compounds inhibited IRS from Staphylococcus aureus WCUH29 more strongly than rat liver IRS.
MeSH terms
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Alkaloids / chemistry
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Animals
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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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Bacteria / drug effects
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Drug Design
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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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Indenes / chemical synthesis*
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Indenes / chemistry*
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Indenes / pharmacology
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Isoleucine-tRNA Ligase / antagonists & inhibitors*
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Kinetics
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Liver / enzymology
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Microbial Sensitivity Tests
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Pyridines*
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Sulfur Compounds*
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Valine-tRNA Ligase / antagonists & inhibitors*
Substances
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Alkaloids
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Indenes
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Pyridines
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SB 203207
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Sulfonamides
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Sulfur Compounds
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altemicidin
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Isoleucine-tRNA Ligase
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Valine-tRNA Ligase