Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate
β-Lactamases comprise the most widely used mode of resistance to β-lactam antibiotics. Cyclic boronates have shown promise as a new class of β-lactamase inhibitor, with pioneering potential to potently inhibit both metallo- and serine-β-lactamases. We report studies concerning a bicyclic boronate es...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2019
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| _version_ | 1797065909198651392 |
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| author | Parkova, A Lucic, A Krajnc, A Brem, J Calvopiña, K Langley, GW McDonough, MA Trapencieris, P Schofield, CJ |
| author_facet | Parkova, A Lucic, A Krajnc, A Brem, J Calvopiña, K Langley, GW McDonough, MA Trapencieris, P Schofield, CJ |
| author_sort | Parkova, A |
| collection | OXFORD |
| description | β-Lactamases comprise the most widely used mode of resistance to β-lactam antibiotics. Cyclic boronates have shown promise as a new class of β-lactamase inhibitor, with pioneering potential to potently inhibit both metallo- and serine-β-lactamases. We report studies concerning a bicyclic boronate ester with a thioether rather than the more typical β-lactam antibiotic “C-6/C-7” acylamino type side chain, which is present in the penicillin/cephalosporin antibiotics. The thioether bicyclic boronate ester was tested for activity against representative serine- and metallo-β-lactamases. The results support the broad inhibition potential of bicyclic boronate based inhibitors with different side chains, including against metallo-β-lactamases from B1, B2, and B3 subclasses. Combined with previous crystallographic studies, analysis of a crystal structure of the thioether inhibitor with the clinically relevant VIM-2 metallo-β-lactamase implies that further SAR work will expand the already broad scope of β-lactamase inhibition by bicyclic boronates.
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| first_indexed | 2024-03-06T21:35:03Z |
| format | Journal article |
| id | oxford-uuid:45f488d6-5bd8-4fac-8d3b-847e41f75e9c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:35:03Z |
| publishDate | 2019 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:45f488d6-5bd8-4fac-8d3b-847e41f75e9c2022-03-26T15:10:54ZBroad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronateJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:45f488d6-5bd8-4fac-8d3b-847e41f75e9cEnglishSymplectic ElementsAmerican Chemical Society2019Parkova, ALucic, AKrajnc, ABrem, JCalvopiña, KLangley, GWMcDonough, MATrapencieris, PSchofield, CJβ-Lactamases comprise the most widely used mode of resistance to β-lactam antibiotics. Cyclic boronates have shown promise as a new class of β-lactamase inhibitor, with pioneering potential to potently inhibit both metallo- and serine-β-lactamases. We report studies concerning a bicyclic boronate ester with a thioether rather than the more typical β-lactam antibiotic “C-6/C-7” acylamino type side chain, which is present in the penicillin/cephalosporin antibiotics. The thioether bicyclic boronate ester was tested for activity against representative serine- and metallo-β-lactamases. The results support the broad inhibition potential of bicyclic boronate based inhibitors with different side chains, including against metallo-β-lactamases from B1, B2, and B3 subclasses. Combined with previous crystallographic studies, analysis of a crystal structure of the thioether inhibitor with the clinically relevant VIM-2 metallo-β-lactamase implies that further SAR work will expand the already broad scope of β-lactamase inhibition by bicyclic boronates. |
| spellingShingle | Parkova, A Lucic, A Krajnc, A Brem, J Calvopiña, K Langley, GW McDonough, MA Trapencieris, P Schofield, CJ Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title | Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title_full | Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title_fullStr | Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title_full_unstemmed | Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title_short | Broad spectrum β-lactamase inhibition by a thioether substituted bicyclic boronate |
| title_sort | broad spectrum β lactamase inhibition by a thioether substituted bicyclic boronate |
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