| Autor: |
Pasquale Linciano, Eleonora Gianquinto, Martina Montanari, Lorenzo Maso, Pierangelo Bellio, Esmeralda Cebrián-Sastre, Giuseppe Celenza, Jesús Blázquez, Laura Cendron, Francesca Spyrakis, Donatella Tondi |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Pharmaceuticals, Vol 13, Iss 3, p 52 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1424-8247 |
| DOI: |
10.3390/ph13030052 |
| Popis: |
The emergence of bacteria that co-express serine- and metallo- carbapenemases is a threat to the efficacy of the available β-lactam antibiotic armamentarium. The 4-amino-1,2,4-triazole-3-thione scaffold has been selected as the starting chemical moiety in the design of a small library of β-Lactamase inhibitors (BLIs) with extended activity profiles. The synthesised compounds have been validated in vitro against class A serine β−Lactamase (SBLs) KPC-2 and class B1 metallo β−Lactamases (MBLs) VIM-1 and IMP-1. Of the synthesised derivatives, four compounds showed cross-class micromolar inhibition potency and therefore underwent in silico analyses to elucidate their binding mode within the catalytic pockets of serine- and metallo-BLs. Moreover, several members of the synthesised library have been evaluated, in combination with meropenem (MEM), against clinical strains that overexpress BLs for their ability to synergise carbapenems. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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