Title: Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans
Authors: Steenackers, Hans ×
Dubey, Akanksha
Robijns, Stijn
Ermolatev, Denis
Delattin, Nicolas
Dovgan, Barbara
Girandon, Lenart
Froehlich, Mirjam
De Brucker, Katrijn
Cammue, Bruno
Thevissen, Karin
Balzarini, Jan
Van der Eycken, Erik
Vanderleyden, Jos #
Issue Date: Oct-2014
Publisher: MDPI AG
Series Title: Molecules vol:19 issue:10 pages:16707-16723
Abstract: Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa). A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs) ranging between 3 and 20. Whereas introduction of a (cyclo-)alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-)alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles.
ISSN: 1420-3049
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Centre of Microbial and Plant Genetics
Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular Design and Synthesis
Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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