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

Int J Mol Sci. 2013 Jun 5;14(6):12054-72. doi: 10.3390/ijms140612054.

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.

MeSH terms

  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biocompatible Materials / pharmacology
  • Biofilms / drug effects*
  • Cell Death / drug effects
  • Cell Line
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / physiology*

Substances

  • Abietanes
  • Anti-Bacterial Agents
  • Biocompatible Materials
  • dehydroabietic acid