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

doi:10.1016/j.bmcl.2014.10.039

Bioorganic & Medicinal Chemistry Letters

Volume 24, Issue 23, 1 December 2014, Pages 5404-5408

https://doi.org/10.1016/j.bmcl.2014.10.039 Get rights and content

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.

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Acknowledgments

V.L., W.J.K. and T.S. are recipients of a fellowship from the Agency for Innovation by Science and Technology (IWT). K.T. acknowledges receipt of a post-doctoral fellowship from the ‘Industrial Research Fund’ (KU Leuven). This work was supported by the Interuniversity Attraction Poles Program initiated by the Belgian Science Policy Office, the European Commission’s seventh Framework Program (FP7/2007–2013) under the grant agreement COATIM (Project no. 278425) and the ‘Industrial Research Fund’

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^†: Present address: Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA.

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

Abstract

Graphical abstract

Section snippets

Acknowledgments

J. Hosp. Infect.

Trends Microbiol.

Anal. Biochem.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Biochem. Pharmacol.

Fitoterapia

J. Pharmacol. Sci.

FEMS Microbiol. Lett.

Cell Host Microbe

Expert Rev. Anti Infect. Ther.

Nat. Rev. Microbiol.

Crit. Care

FEMS Immunol. Med. Microbiol.

J. Am. Chem. Soc.

J. Med. Chem.