First Identification of Boronic Species as Novel Potential Inhibitors of the Staphylococcus aureus NorA Efflux Pump. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Medicinal Chemistry Année : 2014

First Identification of Boronic Species as Novel Potential Inhibitors of the Staphylococcus aureus NorA Efflux Pump.

Fanny Fontaine
  • Fonction : Auteur
Arnaud Hequet
  • Fonction : Auteur
Alexandre Bouillon
  • Fonction : Auteur
Aurélien Lesnard
  • Fonction : Auteur
Claude Jolivalt
  • Fonction : Auteur
Sylvain Rault
  • Fonction : Auteur

Résumé

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.

Domaines

Chimie organique
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Dates et versions

hal-00986332 , version 1 (02-05-2014)

Identifiants

Citer

Fanny Fontaine, Arnaud Hequet, Anne-Sophie Voisin-Chiret, Alexandre Bouillon, Aurélien Lesnard, et al.. First Identification of Boronic Species as Novel Potential Inhibitors of the Staphylococcus aureus NorA Efflux Pump.. Journal of Medicinal Chemistry, 2014, 57 (6), pp.2536-48. ⟨10.1021/jm401808n⟩. ⟨hal-00986332⟩
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