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

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 N-alkylated 3, 6-dih...

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Veröffentlicht in:Bioorganic & Medicinal Chemistry Letters 2014-10, Vol.24 (23), p.5404-5408
Hauptverfasser: Liebens, Veerle, Gerits, Evelien, Knapen, Wouter, Swings, Toon, Beullens, Serge, Steenackers, Hans, Robijns, Stijn, Lippell, A, O'Neill, A, Veber, M, Fröhlich, M, Krona, A, Lövenklev, M, Corbau, Romu, Marchand, Arnaud, Chaltin, Patrick, De Brucker, Katrijn, Thevissen, Karin, Cammue, Bruno, Fauvart, Maarten, Verstraeten, Natalie, Michiels, Jan
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Sprache:eng
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Zusammenfassung: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 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.
ISSN:0960-894X