Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Aβ fibril formation

New bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. These 34 compounds were evaluated by Aβ fibril formation inhibitory assay using thioflavin T as a dye (named ThT assay). Most of them showed excellent inhibitory activities for Aβ fibril formation at IC50 of 0.1–2.7 μM which is comparable to curcumin (IC50 of 0.8 μM). Among them, nine compounds were screened for their cytotoxicities on HT-22 cell by MTT assay at 1, 10, and 50 μM. In particular, I-7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity.

Graphical abstractThe new bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. Most of them showed excellent inhibitory activities for Aβ fibril formation at IC50 of 0.1–2.7 μM which is comparable to curcumin (IC50 of 0.8 μM). In particular, I–7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity.Figure optionsDownload full-size imageDownload as PowerPoint slide