(+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro

Fallarero, Adyary and Skogman, Malena and Kujala, Janni and Rajaratnam, Mohanathas and Moreira, Vânia M. and Yli-Kauhaluoma, Jari and Vuorela, Pia (2013) (+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro. International Journal of Molecular Sciences, 14 (6). pp. 12054-12072. ISSN 1422-0067 (https://doi.org/10.3390/ijms140612054)

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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.

ORCID iDs

Fallarero, Adyary, Skogman, Malena, Kujala, Janni, Rajaratnam, Mohanathas, Moreira, Vânia M. ORCID logoORCID: https://orcid.org/0000-0001-6169-5035, Yli-Kauhaluoma, Jari and Vuorela, Pia;