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Int. J. Mol. Sci. 2013, 14(6), 12054-12072; doi:10.3390/ijms140612054
Article

(+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro

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 and
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1 Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Artillerigatan 6 A, 3rd floor, Biocity, FI-20520, Turku, Finland 2 Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland 3 Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland
* Author to whom correspondence should be addressed.
Received: 26 April 2013 / Revised: 22 May 2013 / Accepted: 29 May 2013 / Published: 5 June 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.
Keywords: anti-biofilm; inhibitor; biofilm; Staphylococcus aureus; abietic acid; natural compounds; phenotypic assays; (+)-dehydroabietic acid; screening anti-biofilm; inhibitor; biofilm; Staphylococcus aureus; abietic acid; natural compounds; phenotypic assays; (+)-dehydroabietic acid; screening
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Fallarero, A.; Skogman, M.; Kujala, J.; Rajaratnam, M.; Moreira, V.M.; Yli-Kauhaluoma, J.; Vuorela, P. (+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro. Int. J. Mol. Sci. 2013, 14, 12054-12072.

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