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- Title
Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors.
- Authors
Ortega-Balleza, Jessica L.; Vázquez-Jiménez, Lenci K.; Ortiz-Pérez, Eyra; Avalos-Navarro, Guadalupe; Paz-González, Alma D.; Lara-Ramírez, Edgar E.; Rivera, Gildardo
- Abstract
Currently, antimicrobial resistance (AMR) is a serious health problem in the world, mainly because of the rapid spread of multidrug-resistant (MDR) bacteria. These include bacteria that produce β-lactamases, which confer resistance to β-lactams, the antibiotics with the most prescriptions in the world. Carbapenems are particularly noteworthy because they are considered the ultimate therapeutic option for MDR bacteria. However, this group of antibiotics can also be hydrolyzed by β-lactamases, including metallo-β-lactamases (MBLs), which have one or two zinc ions (Zn2+) on the active site and are resistant to common inhibitors of serine β-lactamases, such as clavulanic acid, sulbactam, tazobactam, and avibactam. Therefore, the design of inhibitors against MBLs has been directed toward various compounds, with groups such as nitrogen, thiols, and metal-binding carboxylates, or compounds such as bicyclic boronates that mimic hydrolysis intermediates. Other compounds, such as dipicolinic acid and aspergillomarasmin A, have also been shown to inhibit MBLs by chelating Zn2+. In fact, recent inhibitors are based on Zn2+ chelation, which is an important factor in the mechanism of action of most MBL inhibitors. Therefore, in this review, we analyzed the current strategies for the design and mechanism of action of metal-ion-binding inhibitors that combat MDR bacteria.
- Subjects
ZINC ions; CLAVULANIC acid; DRUG resistance in bacteria; DRUG resistance in microorganisms; BICYCLIC compounds; LACTAMS
- Publication
Molecules, 2024, Vol 29, Issue 16, p3944
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules29163944