1-(1H-Indol-3-yl)ethanamine Derivatives as Potent Staphylococcus aureus NorA Efflux Pump Inhibitors.
The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivs., including 12 new compds., was achieved through a series of simple and efficient chem. modifications. These indole derivs. displayed modest or no intrinsic anti-staphylococcal activity. By contrast, several of the compds. restored, in a concn.-dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump. Structure-activity relationships studies revealed that the indolic aldonitrones halogenated at position 5 of the indole core were the most efficient inhibitors of the S. aureus NorA efflux pump. Among the compds., (Z)-N-benzylidene-2-(tert-butoxycarbonylamino)-1-(5-iodo-1H-indol-3-yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin min. inhibitory concn. against the SA-1199B strain when used at a concn. of 0.5 mg.L-1. To the best of our knowledge, this activity is the highest reported to date for an indolic NorA inhibitor. In addn., a new antibacterial compd., tert-Bu (2-(3-hydroxyureido)-2-(1H-indol-3-yl)ethyl)carbamate, which is not toxic for human cells, was also found.
Références
- Titre
- 1-(1H-Indol-3-yl)ethanamine Derivatives as Potent Staphylococcus aureus NorA Efflux Pump Inhibitors.
- Type de publication
- Article de revue
- Année de publication
- 2014
- Auteurs
- Hequet, Arnaud, Burchak Olga N., Jeanty Matthieu, Guinchard Xavier, Le Pihive Emmanuelle, Maigre Laure, Bouhours Pascale, Schneider Dominique, Maurin Max, Paris Jean-Marc, Denis Jean-Noël, and Jolivalt Claude.
- Revue
- ChemMedChem
- Volume
- 9
- Pagination
- 1534–1545
- ISSN
- 1860-7179
Soumis le 12 avril 2018