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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

1
, 1
, 1
, 2
, 2
, 2
 and 1,3,*
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 Bioactives and Nutraceuticals)
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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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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