Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors
Abstract
:1. Introduction
2. Beta (β)-Lactam and Carbapenem Antibiotics
3. Beta(β)-Lactamases
4. Metallo-Beta-Lactamases (MBLs) as Drug Targets
5. MBL Inhibitors
5.1. Metal-Complex-Forming Inhibitors
5.2. Formation of Ternary Complexes
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitor | MIC Meropenem (mg/L) | ||
---|---|---|---|
MP30-63 blaNDM-1 | MP30-57 blaVIM-2 | MP30-58 blaIMP-26 | |
No inhibitor control | 32 | 0.5 | 2 |
44 | 1 | 0.06 | 0.25 |
45 | 1 | 0.06 | 0.5 |
46 | 4 | 0.25 | 4 |
49 | 1 | 0.125 | 2 |
50 | 0.5 | 0.125 | 0.5 |
Inhibitor | pIC50 | |||
---|---|---|---|---|
VIM-1 | NDM-1 | VIM-2 | IMP-1 | |
Bicyclic boronate | 7.1 | 7.5 | 8.5 | 6.0 |
TAN | 8.1 | 8.0 | 8.3 | 5.6 |
57 | 6.9 | 8.1 | 7.7 | 9.2 |
58 | 6.9 | 8.2 | 7.5 | 8.9 |
59 | 7.1 | 7.9 | 6.8 | 8.6 |
60 | 6.5 | 7.9 | 6.7 | 9 |
61 | 7.1 | 8.1 | 7.8 | 8.9 |
62 | 7.4 | 7.9 | 7.3 | 8.2 |
63 | 8.5 | 6.5 | 7.9 | 7.3 |
64 | 6.6 | 8.8 | 6.8 | >9.2 |
65 | 7.4 | 7.9 | 8.2 | 8.3 |
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Ortega-Balleza, J.L.; Vázquez-Jiménez, L.K.; Ortiz-Pérez, E.; Avalos-Navarro, G.; Paz-González, A.D.; Lara-Ramírez, E.E.; Rivera, G. Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors. Molecules 2024, 29, 3944. https://doi.org/10.3390/molecules29163944
Ortega-Balleza JL, Vázquez-Jiménez LK, Ortiz-Pérez E, Avalos-Navarro G, Paz-González AD, Lara-Ramírez EE, Rivera G. Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors. Molecules. 2024; 29(16):3944. https://doi.org/10.3390/molecules29163944
Chicago/Turabian StyleOrtega-Balleza, Jessica L., Lenci K. Vázquez-Jiménez, Eyra Ortiz-Pérez, Guadalupe Avalos-Navarro, Alma D. Paz-González, Edgar E. Lara-Ramírez, and Gildardo Rivera. 2024. "Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors" Molecules 29, no. 16: 3944. https://doi.org/10.3390/molecules29163944