Aza-boronic acids as non-beta-lactam inhibitors of AmpC-beta-lactamase

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3979-83. doi: 10.1016/j.bmcl.2004.05.054.

Abstract

With the aim of improving the ability of non-beta-lactam inhibitors to inhibit AmpC-beta-lactamase, a series of 3-aza-phenyl-boronic acid derivatives was obtained using in parallel synthesis. The molecules were tested against Escherichia coli AmpC-beta-lactamase. The best inhibitors, 3-(2-hydroxy-naphthalen-1-ylazo)-phenyl-boronic acid (12) and 3-(2,4-dihydroxy-naphthalen-1-ylazo)-phenyl-boronic acid (14), showed apparent inhibition constant values (K(i)) of 0.3 and 0.45 microM and increased the potency of the semi-synthetic cephalosporin antibiotic, ceftazidime, lowering its minimum inhibitory concentration (MIC) value of 50%, against Gram-negative bacteria strains, producing high levels of AmpC-beta-lactamase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Boronic Acids / chemical synthesis*
  • Boronic Acids / pharmacology
  • Clavulanic Acid / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Molecular Structure
  • beta-Lactamase Inhibitors*
  • beta-Lactamases

Substances

  • Aza Compounds
  • Bacterial Proteins
  • Boronic Acids
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • Clavulanic Acid
  • AmpC beta-lactamases
  • beta-Lactamases