Approved Drugs Containing Thiols as Inhibitors of Metallo-beta-lactamases: Strategy To Combat Multidrug-Resistant Bacteria.
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Klingler FM, Wichelhaus TA, Frank D, Cuesta-Bernal J, El-Delik J, Muller HF, Sjuts H, Gottig S, Koenigs A, Pos KM, Pogoryelov D, Proschak E
Approved Drugs Containing Thiols as Inhibitors of Metallo-beta-lactamases: Strategy To Combat Multidrug-Resistant Bacteria.
J Med Chem. 2015 Apr 23;58(8):3626-30. doi: 10.1021/jm501844d. Epub 2015 Apr 13.
- PubMed ID
- 25815530 [ View in PubMed]
- Abstract
Resistance to beta-lactam antibiotics can be mediated by metallo-beta-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of beta-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods, we identified drugs that restored the activity of imipenem.