title: Aza-boronic acids as non-beta-lactam inhibitors of AmpC-beta-lactamase.
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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Buzzoni
authors.forename: Jesus
authors.initials: J
authors.lastname: Blazquez
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: Samuele
authors.initials: S
authors.lastname: Calò
authors.forename: Alberto
authors.initials: A
authors.lastname: Venturelli
authors.forename: M Paola
authors.initials: MP
authors.lastname: Costi
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D019818:Clavulanic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D015394:Molecular Structure; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases
chemical_list: D001372:Aza Compounds; D001426:Bacterial Proteins; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; C048795:AmpC beta-lactamases; D001618:beta-Lactamases