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Identification and characterization of an anti-pseudomonal dichlorocarbazol derivative displaying anti-biofilm activity.

Authors :
Liebens V
Gerits E
Knapen WJ
Swings T
Beullens S
Steenackers HP
Robijns S
Lippell A
O'Neill AJ
Veber M
Fröhlich M
Krona A
Lövenklev M
Corbau R
Marchand A
Chaltin P
De Brucker K
Thevissen K
Cammue BP
Fauvart M
Verstraeten N
Michiels J
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Dec 01; Vol. 24 (23), pp. 5404-8.
Publication Year :
2014

Abstract

Pseudomonas aeruginosa strains resistant towards all currently available antibiotics are increasingly encountered, raising the need for new anti-pseudomonal drugs. We therefore conducted a medium-throughput screen of a small-molecule collection resulting in the identification of the N-alkylated 3,6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol (MIC = 18.5 μg mL⁻¹). This compound, compound 1, is bacteriostatic towards a broad spectrum of Gram-positive and Gram-negative pathogens, including P. aeruginosa. Importantly, 1 also eradicates mature biofilms of P. aeruginosa. 1 displays no cytotoxicity against various human cell types, pointing to its potential for further development as a novel antibacterial drug.

Details

Language :
English
ISSN :
1464-3405
Volume :
24
Issue :
23
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
25453797
Full Text :
https://doi.org/10.1016/j.bmcl.2014.10.039