Abstract
The production of metallo-β-lactamases is the most important strategy by which pathogenic bacteria become resistant to currently known β-lactam antibiotics. The emergence of these enzymes is particularly concerning for the future treatment of bacterial infections. There are no clinically available drugs capable of inhibiting any of the metallo-β-lactamases, so there is an urgent need to find such inhibitors. In this review, an up-to-date status of the inhibitors investigated for the inhibition of metallo-β-lactamases has been given so that this rich source of structural information of presently known metallo-β-lactamases could be helpful in generating a broad-spectrum potent inhibitor of metallo-β-lactamases.
Highlights
H O CO2HIt was found that substitution at the 4ʹ-position of the BPT further increased the inhibitory activity of the BPTs. Figure 5 shows the IC50 values comparison of the parent BPT and the substituted BPTs. To further explore the potency of BPTs as MBLs inhibitors, in 1999, Toney et al, [26] screened a series of BPTs containing 3-n-butyl-1-phenylpyrazole-5-carboxylate against B. fragilis and IMP-1 metallo-βlactamases
Introduction βLactam antibiotics are the most widely used antibacterial agents for treating bacterial infections
We discuss currently available MBL inhibitors from different groups to provide a collective view of the chemical structures of these inhibitors, which could be helpful in designing inhibitors capable of meeting the serious biological threat, resistance of pathogenic bacteria to β-lactam antibiotics
Summary
It was found that substitution at the 4ʹ-position of the BPT further increased the inhibitory activity of the BPTs. Figure 5 shows the IC50 values comparison of the parent BPT and the substituted BPTs. To further explore the potency of BPTs as MBLs inhibitors, in 1999, Toney et al, [26] screened a series of BPTs containing 3-n-butyl-1-phenylpyrazole-5-carboxylate against B. fragilis and IMP-1 metallo-βlactamases. Vella et al, [2] recently screened a 500 compound MaybridgeTM library for several new classes of leading inhibitors against the IMP-1 MBL, and considered the 4-methyl-5(trifluoromethyl)-4H-1,2,4-triazole-3-thiol 50 (Ki = 0.97 ± 0.60 mM) the most promising for further study We elaborated this ring system to increase the potency of this compound and identified the mercapto triazole 51 as showing mixed inhibition (Ki competitive = 75 ± 30 μM and Ki uncompetitive = 56 ± 10 μM) for the IMP-1 enzyme.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
