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Isonitrile-based multicomponent synthesis of β-amino boronic acids as β-lactamase inhibitors

  • Bassini, Emanuele Dipartimento di Chimica, Università degli Studi di Milano, Italy
  • Gazzotti, Stefano Dipartimento di Chimica, Università degli Studi di Milano, Italy
  • Sannio, Filomena Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Italy
  • Lo Presti, Leonardo Dipartimento di Chimica, Università degli Studi di Milano, Italy
  • Sgrignani, Jacopo Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Docquier, Jean-Denis Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Italy
  • Grazioso, Giovanni Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Italy
  • Silvani, Alessandra Dipartimento di Chimica, Università degli Studi di Milano, Italy
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    12.05.2020
Published in:
  • Antibiotics. - 2020, vol. 9, no. 5, p. 21 p
Multicomponent reactions
β-amino boronic acids
β-lactamases
Covalent docking
English The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study.
Language
  • English
Classification
Pharmacology, therapeutics, toxicology
License
CC BY
Open access status
gold
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Persistent URL
https://n2t.net/ark:/12658/srd1319214
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