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

With the aim of improving the ability of non-p-lactam inhibitors to inhibit AmpC-beta-tactamase, 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 muM 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-p-lactamase. (C) 2004 Elsevier Ltd. All rights reserved.