Academic Journal
Virtual screening identifies broad-spectrum β-lactamase inhibitors with activity on clinically relevant serine- and metallo-carbapenemases
| العنوان: | Virtual screening identifies broad-spectrum β-lactamase inhibitors with activity on clinically relevant serine- and metallo-carbapenemases |
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| المؤلفون: | Spyrakis F., Santucci M., Maso L., Cross S., Gianquinto E., Sannio F., Verdirosa F., De Luca F., Docquier J. -D., Cendron L., Tondi D., Venturelli A., Cruciani G., Costi M. P. |
| المساهمون: | Spyrakis F., Santucci M., Maso L., Cross S., Gianquinto E., Sannio F., Verdirosa F., De Luca F., Docquier J.-D., Cendron L., Tondi D., Venturelli A., Cruciani G., Costi M.P. |
| سنة النشر: | 2020 |
| المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| الوصف: | Bacteria are known to evade β-lactam antibiotic action by producing β-lactamases (BLs), including carbapenemases, which are able to hydrolyze nearly all available β-lactams. The production of BLs represents one of the best known and most targeted mechanisms of resistance in bacteria. We have performed the parallel screening of commercially available compounds against a panel of clinically relevant BLs: class A CTX-M-15 and KPC-2, subclass B1 NDM-1 and VIM-2 MBLs, and the class C P. aeruginosa AmpC. The results show that all BLs prefer scaffolds having electron pair donors: KPC-2 is preferentially inhibited by sulfonamide and tetrazole-based derivatives, NDM-1 by compounds bearing a thiol, a thiosemicarbazide or thiosemicarbazone moiety, while VIM-2 by triazole-containing molecules. Few broad-spectrum BLs inhibitors were identified; among these, compound 40 potentiates imipenem activity against an NDM-1-producing E. coli clinical strain. The binary complexes of the two most promising compounds binding NDM-1 and VIM-2 were obtained at high resolution, providing strong insights to improve molecular docking simulations, especially regarding the interaction of MBLs with inhibitors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000556388300017; volume:10; issue:12763; firstpage:1; lastpage:15; numberofpages:15; journal:SCIENTIFIC REPORTS; http://hdl.handle.net/2318/1765330; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85088710021 |
| DOI: | 10.1038/s41598-020-69431-y |
| الاتاحة: | http://hdl.handle.net/2318/1765330 https://doi.org/10.1038/s41598-020-69431-y |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.456A422 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-020-69431-y |
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