Approved Drugs Containing Thiols as Inhibitors of Metallo-β-lactamases: Strategy To Combat Multidrug-Resistant Bacteria

Autor:	Müller Hf, Stephan Göttig, Ewgenij Proschak, Cuesta-Bernal J, Denia Frank, Arno Koenigs, Klaas M. Pos, Franca-Maria Klingler, Hanno Sjuts, Jasmin El-Delik, Thomas A. Wichelhaus, Denys Pogoryelov
Rok vydání:	2015
Předmět:	Models Molecular Imipenem medicine.drug_class Antibiotics Antimicrobial susceptibility Pharmacology Crystallography X-Ray beta-Lactams beta-Lactam Resistance beta-Lactamases Metallo β lactamase Drug Resistance Multiple Bacterial Drug Discovery Escherichia coli polycyclic compounds Screening method medicine Humans Pseudomonas Infections Sulfhydryl Compounds Escherichia coli Infections chemistry.chemical_classification biochemical phenomena metabolism and nutrition bacterial infections and mycoses Anti-Bacterial Agents Klebsiella Infections Klebsiella pneumoniae Enzyme Multidrug resistant bacteria chemistry Pseudomonas aeruginosa Molecular Medicine beta-Lactamase Inhibitors medicine.drug
Zdroj:	Journal of Medicinal Chemistry. 58:3626-3630
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm501844d
Popis:	Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1e1cd8f6aff3d6af7b0a63cc54e772d https://doi.org/10.1021/jm501844d Zobrazit plný text záznamu