First Identification of Boronic Species as Novel Potential Inhibitors of the Staphylococcus aureus NorA Efflux Pump
| Autor: | Alexandre Bouillon, Aurélien Lesnard, Sylvain Rault, Thierry Cresteil, Arnaud Hequet, Fanny Fontaine, Anne Sophie Voisin-Chiret, Claude Jolivalt |
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| Přispěvatelé: | Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ) |
| Rok vydání: | 2014 |
| Předmět: |
inorganic chemicals
Staphylococcus aureus Cell Survival medicine.drug_class Antibiotics Antineoplastic Agents Microbial Sensitivity Tests medicine.disease_cause KB Cells Bacterial cell structure Microbiology Structure-Activity Relationship Antibiotic resistance Bacterial Proteins Ciprofloxacin [ CHIM.ORGA ] Chemical Sciences/Organic chemistry Drug Resistance Bacterial Drug Discovery medicine Humans [CHIM.ORGA]Chemical Sciences/Organic chemistry Chemistry Biological activity Antimicrobial Boronic Acids Anti-Bacterial Agents Culture Media 3. Good health Biochemistry Molecular Medicine Indicators and Reagents Efflux Drug Screening Assays Antitumor Multidrug Resistance-Associated Proteins medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2014, 57 (6), pp.2536-48. ⟨10.1021/jm401808n⟩ Journal of Medicinal Chemistry, American Chemical Society, 2014, 57 (6), pp.2536-48. 〈10.1021/jm401808n〉 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | International audience; Overexpression of efflux pumps is an important mechanism of bacterial resistance that results in the extrusion of antimicrobial agents outside the bacterial cell. Inhibition of such pumps appears to be a promising strategy that could restore the potency of existing antibiotics. The NorA efflux pump of Staphylococcus aureus confers resistance to a wide range of unrelated substrates, such as hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype. In this work, approximately 150 heterocyclic boronic species were evaluated for their activity against susceptible and resistant strains of S. aureus. Twenty-four hit compounds, although inactive when tested alone, were found to potentiate ciprofloxacin activity by a 4-fold increase at concentrations ranging from 0.5 to 8 μg/mL against S. aureus 1199B, which overexpresses NorA. Boron-free analogues showed no biological activity, thus revealing that the boron atom is crucial for biological activity. This work describes the first reported efflux pump inhibitory activity of boronic acid derivatives. |
| Databáze: | OpenAIRE |
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