Anthranilate 4H-oxazol-5-ones: novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):37-41. doi: 10.1016/j.bmcl.2003.10.032.

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

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / enzymology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Microbial Sensitivity Tests / statistics & numerical data
  • Protein Synthesis Inhibitors / chemistry*
  • Protein Synthesis Inhibitors / pharmacology
  • Transferases (Other Substituted Phosphate Groups) / antagonists & inhibitors*
  • Transferases (Other Substituted Phosphate Groups) / metabolism
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Protein Synthesis Inhibitors
  • ortho-Aminobenzoates
  • anthranilic acid
  • Transferases (Other Substituted Phosphate Groups)
  • holo-(acyl-carrier-protein) synthase