title: (+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro.
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.
authors.affiliation: Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Artillerigatan 6 A, 3rd floor, Biocity, FI-20520, Turku, Finland. pia.vuorela@abo.fi.
authors.forename: Adyary
authors.initials: A
authors.lastname: Fallarero
authors.forename: Malena
authors.initials: M
authors.lastname: Skogman
authors.forename: Janni
authors.initials: J
authors.lastname: Kujala
authors.forename: Mohanathas
authors.initials: M
authors.lastname: Rajaratnam
authors.forename: Vânia M
authors.initials: VM
authors.lastname: Moreira
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*
chemical_list: D045784:Abietanes; D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; C013913:dehydroabietic acid