دورية أكاديمية
Phenylboronic Acids Probing Molecular Recognition against Class A and Class C beta-Lactamases
| العنوان: | Phenylboronic Acids Probing Molecular Recognition against Class A and Class C beta-Lactamases |
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| المؤلفون: | Linciano P., Vicario M., Kekez I., Bellio P., Celenza G., Martin-Blecua I., Blazquez J., Cendron L., Tondi D. |
| المساهمون: | Linciano, P., Vicario, M., Kekez, I., Bellio, P., Celenza, G., Martin-Blecua, I., Blazquez, J., Cendron, L., Tondi, D. |
| سنة النشر: | 2019 |
| المجموعة: | IRIS UNIPV (Università degli studi di Pavia) |
| مصطلحات موضوعية: | Boronic acid, Carbapenemase, Enzyme inhibitor, GES-5 guyana extended-spectrum-lactamase, KPC-2 klebsiella pneumoniae, Serine β-lactamase, Synergism, X-ray crystallography |
| الوصف: | Worldwide dissemination of pathogens resistant to almost all available antibiotics represent a real problem preventing efficient treatment of infectious diseases. Among antimicrobial used in therapy, Β-lactam antibiotics represent 40% thus playing a crucial role in the management of infections treatment. We report a small series of phenylboronic acids derivatives (BAs) active against class A carbapenemases KPC-2 and GES-5, and class C cephalosporinases AmpC. The inhibitory profile of our BAs against class A and C was investigated by means of molecular docking, enzyme kinetics and X-ray crystallography. We were interested in the mechanism of recognition among class A and class C to direct the design of broad serine Β-Lactamases (SBLs) inhibitors. Molecular modeling calculations vs GES-5 and crystallographic studies vs AmpC reasoned, respectively, the ortho derivative 2 and the meta derivative 3 binding affinity. The ability of our BAs to protect Β-lactams from BLs hydrolysis was determined in biological assays conducted against clinical strains: Fractional inhibitory concentration index (FICI) tests confirmed their ability to be synergic with Β-lactams thus restoring susceptibility to meropenem. Considering the obtained results and the lack of cytotoxicity, our derivatives represent validated probe for the design of SBLs inhibitors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31574990; info:eu-repo/semantics/altIdentifier/wos/WOS:000506678800016; volume:8; issue:171; firstpage:1; lastpage:15; numberofpages:5; journal:ANTIBIOTICS; http://hdl.handle.net/11571/1462632Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85074901383; https://www.mdpi.com/2079-6382/8/4/171/pdfTest |
| DOI: | 10.3390/antibiotics8040171 |
| الإتاحة: | https://doi.org/10.3390/antibiotics8040171Test http://hdl.handle.net/11571/1462632Test https://www.mdpi.com/2079-6382/8/4/171/pdfTest |
| رقم الانضمام: | edsbas.C6A57B49 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/antibiotics8040171 |
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