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Updated: Sep 16, 2025
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Development and in vitro evaluation of 1,4,7-triazacyclononane-coupled β-lactams against metallo-β-lactamase
Mbongeni Shungube1, Nakita Reddy1,2, Terisha Ghazi3
1Catalysis and Peptide Research Unit, University of KwaZulu-Natal Durban 4001 South Africa govenderthav@icloud.com naickert1@ukzn.ac.za +27 312601845.
Abstract:
Antimicrobial resistance (AMR) is a critical global issue, particularly against β-lactam antibiotics, which comprise over 60% of prescriptions. Metallo-β-lactamases (MBLs) are especially concerning as they inactivate nearly all β-lactams, except monobactams. Unlike serine-β-lactamases (SBLs), for which inhibitors exist, there are no clinically approved MBL inhibitors; only taniborbactam is in pre-registration. This study introduces eight new MBL inhibitors (13a-f, 14a-b), designed using a 1,4,7-triazacyclononane (NO3PY) chelator linked to a β-lactam. These inhibitors restored the efficacy of meropenem, reducing its minimum inhibitory concentration (MIC) against MBL-expressing pathogens to <2 mg L-1. Time-kill assays confirmed bactericidal activity, with this series being non-toxic and highly specific, these compounds hold promising potential as MBL inhibitors.
