Abstract
D-optimal design and Projection to Latent Structures (PLS) analysis were used to optimize screening hit 5 (B. subtilis AcpS IC(50): 15 microM, B. subtilis MIC: >200 microM) into a series of 4H-oxazol-5-one, small molecule, antibacterial, AcpS inhibitors. Specifically, 15, 16 and 18 show microM or sub-microM AcpS inhibition (IC(50)s: 15: 1.1 microM, 16: 1.5 microM, 18: 0.27 microM) and moderate antibacterial activity (MICs: 12.5-50 microM) against B. subtilis, E. faecalis ATCC, E. faecalis VRE and S. pneumo+.
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Bacillus subtilis / enzymology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Microbial Sensitivity Tests / statistics & numerical data
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Protein Synthesis Inhibitors / chemistry*
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Protein Synthesis Inhibitors / pharmacology
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Transferases (Other Substituted Phosphate Groups) / antagonists & inhibitors*
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Transferases (Other Substituted Phosphate Groups) / metabolism
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ortho-Aminobenzoates / chemistry*
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ortho-Aminobenzoates / pharmacology
Substances
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Protein Synthesis Inhibitors
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ortho-Aminobenzoates
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anthranilic acid
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Transferases (Other Substituted Phosphate Groups)
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holo-(acyl-carrier-protein) synthase