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Phenotypic Screening Applied to the Anti-biofilm Drug Discovery: Identification of Anti-biofilm Flavonoids from a Chemical Library
EP22734
Poster Title: Phenotypic Screening Applied to the Anti-biofilm Drug Discovery: Identification of Anti-biofilm Flavonoids from a Chemical Library
Submitted on 23 Feb 2015
Author(s): Suvi Manner1*, Malena Skogman2, Pia Vuorela2, Adyary Fallarero2
Affiliations: 1Pharmaceutical Sciences, Department of Biosciences, Åbo Akademi University, Finland 2Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Finland
This poster was presented at Screening Europe 2015
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Abstract: Biofilms are recognized as a main cause of chronic and antibiotic-resistant infections. However, there is not any specific treatment available for biofilms, so the need for new anti-biofilms is enormous. Flavonoids are among the most widely studied natural compounds with diverse biological in vitro and in vivo activities, including antibacterial activity. However, fewer reports have studied their anti-biofilm properties1. In this work, a commercial collection of 500 flavonoids was screened for the anti-biofilm activity utilizing a two-phased high-throughput screening (HTS) platform consisting of three phenotypic assays, previously optimized for screening of natural compound libraries against Staphylococcus aureus biofilms 2-5. After the initial screening, flavonoids were classified as inactive (443), moderately active (47) or highly active (10). Further, selection process combining bioactivity and selectivity identified two flavans as the most promising. Altogether, this work offers an improved methodological workflow for anti-biofilm screens of chemical libraries taking into account connections between anti-biofilm and antibacterial properties. Moreover, it provides a large amount of new bioactivity data of flavonoids and characterizes two synthetic flavans as potent anti-biofilms with ability to act on existing biofilms at low micromolar concentrations (27.9 and 60.5 μM) but also on suspended bacteria.Summary: This work represents a systematic exploration of a flavonoids collection for the inhibitory activity against Staphylococcus aureus biofilms and offers an improved methodological workflow for anti-biofilm screens of chemical libraries taking into account the connections between anti-biofilm and antibacterial properties.References: 1) Cushnie TP and Lamb AJ. Int J Antimicrob Agents 2011; 38:99-107.
2) Manner S, et al. Int J Mol Sci 2013; 14:19434-51.
3) Sandberg M, et al. Int J Antimicrob Agents 2008; 32:233-40.
4) Sandberg ME, et al. J Microbiol Methods 2009; 78:104-6.
5) Skogman ME, et al. J Antibiot (Tokyo) 2012; 65:453-459.
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