Beta-lactam antibiotics are one of the most commonly used drug classes in managing bacterial infections. However, their use is threatened by the alarming phenomenon of antimicrobial resistance, which represents a worldwide health concern. Given the continuous spread of metallo-β-lactamases (MBLs) producing pathogens, the need to discover broad-spectrum β-lactamase inhibitors is increasingly growing. A series of zinc chelators have been synthesized and investigated for their ability to hamper the Zn-ion network of interactions in the active site of MBLs. We assessed the inhibitory activity of new polyimidazole ligands N,N'-bis((imidazol-4-yl)methyl)-ethylenediamine, N,N,N'-tris((imidazol-4-yl)methyl)-ethylenediamine, N,N,N,N'-tetra((imidazol-4-yl-methyl)-ethylenediamine toward three different subclasses B1 MBLs: VIM-1, NDM-1 and IMP-1 by in vitro assays. The activity of known zinc chelators such as 1,4,7,10,13-Pentaazacyclopentadecane, 1,4,8,11-Tetraazacyclotetradecane and 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid was also assessed. Moreover, a molecular docking study was carried to gain insight into the interaction mode of the most active ligands.
New polyimidazole ligands against subclass B1 metallo-β-lactamases: Kinetic, microbiological, docking analysis
Di Bella, Stefano;
2023-01-01
Abstract
Beta-lactam antibiotics are one of the most commonly used drug classes in managing bacterial infections. However, their use is threatened by the alarming phenomenon of antimicrobial resistance, which represents a worldwide health concern. Given the continuous spread of metallo-β-lactamases (MBLs) producing pathogens, the need to discover broad-spectrum β-lactamase inhibitors is increasingly growing. A series of zinc chelators have been synthesized and investigated for their ability to hamper the Zn-ion network of interactions in the active site of MBLs. We assessed the inhibitory activity of new polyimidazole ligands N,N'-bis((imidazol-4-yl)methyl)-ethylenediamine, N,N,N'-tris((imidazol-4-yl)methyl)-ethylenediamine, N,N,N,N'-tetra((imidazol-4-yl-methyl)-ethylenediamine toward three different subclasses B1 MBLs: VIM-1, NDM-1 and IMP-1 by in vitro assays. The activity of known zinc chelators such as 1,4,7,10,13-Pentaazacyclopentadecane, 1,4,8,11-Tetraazacyclotetradecane and 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid was also assessed. Moreover, a molecular docking study was carried to gain insight into the interaction mode of the most active ligands.File | Dimensione | Formato | |
---|---|---|---|
BOGNANNI JIB 2023.pdf
Accesso chiuso
Tipologia:
Documento in Versione Editoriale
Licenza:
Copyright Editore
Dimensione
2.8 MB
Formato
Adobe PDF
|
2.8 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
1-s2.0-S0162013423000454-mmc1.pdf
Accesso chiuso
Descrizione: Supplementary data
Tipologia:
Altro materiale allegato
Licenza:
Digital Rights Management non definito
Dimensione
355.11 kB
Formato
Adobe PDF
|
355.11 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
BOGNANNI+JIB+2023-Post_print.pdf
embargo fino al 21/02/2025
Tipologia:
Bozza finale post-referaggio (post-print)
Licenza:
Creative commons
Dimensione
3.22 MB
Formato
Adobe PDF
|
3.22 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.