Klingler Franca-M, Wichelhaus Thomas A, Frank Denia, Cuesta-Bernal Jenifer, El-Delik Jasmin, Müller H Florian, Sjuts Hanno, Göttig Stephan, Koenigs Arno, Pos Klaas M, Pogoryelov Denys, Proschak Ewgenij
§Institute of Medical Microbiology and Infection Control, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany.
J Med Chem. 2015 Apr 23;58(8):3626-30. doi: 10.1021/jm501844d. Epub 2015 Apr 13.
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.
对β-内酰胺类抗生素的耐药性可由金属β-内酰胺酶（MBL）介导。一种MBL抑制剂可以恢复β-内酰胺类药物的有效性。我们报告了对已批准的含硫醇药物作为NDM-1、VIM-1和IMP-7抑制剂的评估。通过使用可购买的荧光底物和热位移的新型测定法对药物进行评估。在抗菌药敏试验中测试了最佳化合物。使用这些正交筛选方法，我们鉴定出了能恢复亚胺培南活性的药物。
