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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Targeting clinically-relevant metallo-β-lactamases: from high-throughput docking to broad-spectrum inhibitors
Margherita Brindisi1,2, Simone Brogi1,2, Simone Giovani1,2
1a European Research Centre for Drug Discovery and Development (NatSynDrugs), University of Siena , Siena , Italy.
Abstract:
Metallo-β-lactamases (MBLs) represent one of the most important and widespread mechanisms of resistance to β-lactam antibiotics (including the life-saving carbapenems), against which no clinically useful inhibitors are currently available. We report herein a structure-based high-throughput docking (HTD) campaign on three clinically-relevant acquired MBLs (IMP-1, NDM-1 and VIM-2). The initial hit NF1810 (1) was optimized providing the broad-spectrum inhibitor 3i, which is able to potentiate the in vitro activity of cefoxitin on a VIM-2-producing E. coli strain.
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