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
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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.
Fallarero A, Skogman M, Kujala J, Rajaratnam M, Moreira VM, Yli-Kauhaluoma J, Vuorela P. (+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro. International Journal of Molecular Sciences. 2013; 14(6):12054-12072.
Fallarero, Adyary; Skogman, Malena; Kujala, Janni; Rajaratnam, Mohanathas; Moreira, Vânia M.; Yli-Kauhaluoma, Jari; Vuorela, Pia. 2013. "(+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro." Int. J. Mol. Sci. 14, no. 6: 12054-12072.