Tauopathies, such as Alzheimer's disease, have been the subject of several hypotheses regarding the way to treat them. Hyperphosphorylation of tau protein leading to its aggregation is widely recognized as a key step in the development of these diseases resulting in neuronal dysfunction. The AcPHF6 model of tau that includes the shorter critical fragment involved in the protein aggregation was used in vitro to identify new potential inhibitors. Following a previous study on aurone derivatives, we herein compare this polyphenol family to a very close one, the benzylidene-2,3-dihydro-1H-inden-1-one (also named indanone). The structure activity relationship studies bring to light the importance of the hydroxylation pattern in both series: the more hydroxylated, the more active. In addition, the three-dimensional shape of the molecules is involved in their interaction mode with their target, thus defining their role either as inhibitors of fiber elongation or as fiber-binding molecules. Indanone 13a was identified as a promising inhibitor: its activity was confirmed by circular dichroism and atomic force microscopy studies.

Tauopathies，如阿尔茨海默病，一直是关于治疗方法的几个假设的主题。tau 蛋白的过度磷酸化导致其聚集被广泛认为是这些疾病发展的关键步骤，导致神经元功能障碍。包含参与蛋白质聚集的较短关键片段的 tau 的 AcPHF6 模型在体外用于鉴定新的潜在抑制剂。在先前对 aurone 衍生物的研究之后，我们在此将这个多酚家族与一个非常接近的多酚家族进行了比较，即 benzylidene-2,3-dihydro-1 H-inden-1-one（也称为茚满酮）。结构活性关系研究揭示了两个系列中羟基化模式的重要性：羟基化越多，活性越高。此外，分子的三维形状与它们与靶标的相互作用模式有关，因此定义了它们作为纤维伸长抑制剂或纤维结合分子的作用。茚满酮13a被确定为一种有前途的抑制剂：其活性已通过圆二色性和原子力显微镜研究得到证实。