Structure-based approach for identification of novel phenylboronic acids as serine-β-lactamase inhibitors
Articolo
Data di Pubblicazione:
2016
Citazione:
Structure-based approach for identification of novel phenylboronic acids as serine-β-lactamase inhibitors / J. Sgrignani, F. de Luca, H. Torosyan, J. Docquier, D. Duan, B. Novati, F. Prati, G. Colombo, G. Grazioso. - In: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN. - ISSN 0920-654X. - 30:10(2016), pp. 851-861. [10.1007/s10822-016-9962-8]
Abstract:
β-Lactamases are bacterial enzymes conferring resistance to β-lactam antibiotics in clinically-relevant pathogens, and represent relevant drug targets. Recently, the identification of new boronic acids (i.e. RPX7009) paved the way to the clinical application of these molecules as potential drugs. Here, we screened in silico a library of ~1400 boronic acids as potential AmpC β-lactamase inhibitors. Six of the most promising candidates were evaluated in biochemical assays leading to the identification of potent inhibitors of clinically-relevant β-lactamases like AmpC, KPC-2 and CTX-M-15. One of the selected compounds showed nanomolar Ki value with the clinically-relevant KPC-2 carbapenemase, while another one exhibited broad spectrum inhibition, being also active on Enterobacter AmpC and the OXA-48 class D carbapenemase.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Antibiotic resistance; Beta-lactamase; Boronic acids; Carbapenemase; Docking; Extended-spectrum β-lactamase; Virtual screening; Drug Discovery3003 Pharmaceutical Science; Computer Science Applications1707 Computer Vision and Pattern Recognition; Physical and Theoretical Chemistry
Elenco autori:
J. Sgrignani, F. de Luca, H. Torosyan, J. Docquier, D. Duan, B. Novati, F. Prati, G. Colombo, G. Grazioso
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