Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against -Lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of -Lactamases has been here structurally investigated. An extensive x-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo -Lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recogni-tion, especially in the interaction with MBLs. Our derivatives are the first case of non-cyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.

X-ray-crystallography deciphers the activity of broad spectrum boronic acid β-Lactamases inhibitors / Cendron, Laura; Quotadamo, Antonio; Maso, Lorenzo; Bellio, Pierangelo; Montanari, Martina; Celenza, Giuseppe; Venturelli, Alberto; Costi, Maria Paola; Tondi, Donatella. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 10:4(2019), pp. 650-655. [10.1021/acsmedchemlett.8b00607]

X-ray-crystallography deciphers the activity of broad spectrum boronic acid β-Lactamases inhibitors

Quotadamo, Antonio
Methodology
;
Venturelli, Alberto;Costi, Maria Paola
Funding Acquisition
;
Tondi, Donatella
Supervision
2019

Abstract

Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against -Lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of -Lactamases has been here structurally investigated. An extensive x-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo -Lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recogni-tion, especially in the interaction with MBLs. Our derivatives are the first case of non-cyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.
27-mar-2019
10
4
650
655
X-ray-crystallography deciphers the activity of broad spectrum boronic acid β-Lactamases inhibitors / Cendron, Laura; Quotadamo, Antonio; Maso, Lorenzo; Bellio, Pierangelo; Montanari, Martina; Celenza, Giuseppe; Venturelli, Alberto; Costi, Maria Paola; Tondi, Donatella. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 10:4(2019), pp. 650-655. [10.1021/acsmedchemlett.8b00607]
Cendron, Laura; Quotadamo, Antonio; Maso, Lorenzo; Bellio, Pierangelo; Montanari, Martina; Celenza, Giuseppe; Venturelli, Alberto; Costi, Maria Paola; Tondi, Donatella
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1173940
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