Fallarero Adyary, Skogman Malena, Kujala Janni, Rajaratnam Mohanathas, Moreira Vânia M, Yli-Kauhaluoma Jari, Vuorela Pia
Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Artillerigatan 6 A, 3rd floor, Biocity, FI-20520, Turku, Finland.
Int J Mol Sci. 2013 Jun 5;14(6):12054-72. doi: 10.3390/ijms140612054.
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.
迫切需要强效药物来对抗细菌生物膜感染，尤其是由革兰氏阳性菌引起的感染，如金黄色葡萄球菌。此外，对于旨在探索生物膜行为和功能的基础体外或体内研究，也需要能够用作化学工具的抗生物膜化合物/试剂。在本论文中，使用我们小组先前发表的由两种表型分析组成的平台，对一系列天然存在的枞酸型二萜及其衍生物进行了针对金黄色葡萄球菌生物膜的测试。鉴定出三种活性化合物：去氢枞胺（1）、（+）-脱氢枞酸（2）和（+）-脱氢枞胺（3），它们在低微摩尔浓度范围内可防止生物膜形成，并且与典型抗生素不同，只需2至4倍高的浓度就能显著降低现有生物膜的活力和生物量。化合物2，（+）-脱氢枞酸，对生物膜细菌具有最高的选择性，具有高杀菌效力（基于对数减少值），并且三种不同的哺乳动物细胞系对其耐受性最佳。由于（+）-脱氢枞酸是一种易于获得的化合物，它在生物膜相关研究中用作分子探针以及作为开发强效候选药物的启发性化学模型具有巨大潜力。
