We recently described multifunctional tools ( 2a– c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with A β aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level.
We determined the inhibitory potency of 2a–c on A β 1–42 self‐aggregation, the interference of 2a with the toxic A β oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of A β toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with A β and with the A β‐preformed fibrils were computationally analyzed. 2a– c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts).