Inhibitors of the FEZ-1 metallo-beta-lactamase.
Metallo-beta-lactamases (MBLs) catalyze the hydrolysis of beta-lactams including penicillins, cephalosporins and carbapenems. Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a K(i) of 6.1+/-0.7microM against the FEZ-1 MBL but does not significantly inhibit the IMP-1, BcII, CphA or L1 MBLs.
Liénard
Benoît M R
BM
Chemistry Research Laboratory, 12 Mansfield Road, Oxford, United Kingdom.
Horsfall
Louise E
LE
Galleni
Moreno
M
Frère
Jean-Marie
JM
Schofield
Christopher J
CJ
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D008024:Ligands; D065093:beta-Lactamase Inhibitors; C434285:beta-lactamase FEZ-1; D001618:beta-Lactamases