Amyloid β (Aβ) aggregation inhibitor activity cliff involving a curcumin structure was predicted using the SAR Matrix method on the basis of 697 known Aβ inhibitors from ChEMBL (data set 2487). Among the compounds predicted, compound B was found to possess approximately 100 times higher inhibitory activity toward Aβ aggregation than curcumin. TEM images indicate that compound B induced the shortening of Aβ fibrils and increased the generation of Aβ oligomers in a concentration dependent manner. Furthermore, compound K, in which the methyl ester of compound B was replaced by the tert-butyl ester, possessed low cytotoxicity on N2A cells and attenuated Aβ-induced cytotoxicity, indicating that compound K would have an ability for preventing neurotoxicity caused by Aβ aggregation.

基于来自 ChEMBL 的 697 种已知 Aβ 抑制剂（数据集 2487），使用 SAR 矩阵方法预测了涉及姜黄素结构的淀粉样蛋白 β (Aβ) 聚集抑制剂活性悬崖。在预测的化合物中，发现化合物B对 Aβ 聚集的抑制活性比姜黄素高约 100 倍。TEM 图像表明化合物B以浓度依赖性方式诱导 Aβ 原纤维缩短并增加 Aβ 寡聚体的产生。此外，化合物K，其中化合物B的甲酯被叔丁酯取代，对N2A细胞具有低细胞毒性并减弱Aβ诱导的细胞毒性，表明化合物K 将具有预防由 Aβ 聚集引起的神经毒性的能力。