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

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.