Department Chemical Microbiology, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.
Department Microbial Drugs, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.
Biomolecules. 2018 Oct 30;8(4):129. doi: 10.3390/biom8040129.
During the course of our ongoing work to discover new inhibitors of biofilm formation of from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent.
在我们从真菌来源中发现新的生物膜形成抑制剂的持续工作过程中，我们首次观察到从子囊菌纲的培养物中分离出的细胞松弛素对生物膜的抑制作用。通过生物测定指导的分级分离程序纯化了两种新化合物；随后通过核磁共振（NMR）光谱和高分辨率质谱（HR-MS）阐明了它们的结构。这一意外发现促使我们进一步测试来自其他真菌和商业来源的细胞松弛素来进行比较。在 21 种细胞松弛素中，有 13 种在亚毒性水平下对生物膜形成显示出显著的抑制作用。这些发现首次表明细胞松弛素有作为生物膜抑制剂的潜力，也因为最小抑菌浓度（MIC）与抗生物膜活性无关。然而，细胞松弛素是肌动蛋白的抑制剂，这使得其中一些对真核细胞非常有毒。由于测试化合物的化学结构相当多样化，因此需要包括其他衍生物，并评估它们对哺乳动物细胞与细菌的选择性，作为下一步以开发构效关系并确定用于开发抗生物膜剂的最佳候选物。
