X-ray Crystallography Deciphers the Activity of Broad-Spectrum Boronic Acid beta-Lactamase Inhibitors.
Cendron, L., Quotadamo, A., Maso, L., Bellio, P., Montanari, M., Celenza, G., Venturelli, A., Costi, M.P., Tondi, D.(2019) ACS Med Chem Lett 10: 650-655
- PubMed: 30996812
- DOI: https://doi.org/10.1021/acsmedchemlett.8b00607
- Primary Citation of Related Structures:
6IBS, 6IBV, 6Q2Y, 6Q30, 6Q35 - PubMed 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 β-lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of β-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 β-lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recognition, especially in the interaction with MBLs. Our derivatives are the first case of noncyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.
Organizational Affiliation:
Department of Biology, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.