- The identification of new metallo-β-lactamase inhibitor leads from fragment-based screening.
The identification of new metallo-β-lactamase inhibitor leads from fragment-based screening.
Bioorganic & medicinal chemistry letters (2011-05-04)
Peter Vella, Waleed M Hussein, Eleanor W W Leung, Daniel Clayton, David L Ollis, Nataša Mitić, Gerhard Schenk, Ross P McGeary
PMID21536436
RESUMEN
The emergence of metallo-β-lactamases (MBLs) capable of hydrolysing a broad spectrum of β-lactam antibiotics is particularly concerning for the future treatment of bacterial infections. This work describes the discovery of lead compounds for the development of new inhibitors using a competitive colorimetric assay based on the chromogenic cephalosporin CENTA, and a 500 compound Maybridge™ library suitable for fragment-based screening. The interactions between identified inhibitory fragments and the active site of the MBL from Klebsiella pneumoniae and Pseudomonas aeruginosa were probed by in silico docking studies.