New potent human acetylcholinesterase inhibitors in the tetracyclic triterpene series with inhibitory potency on amyloid β aggregation

New acetylcholinesterase inhibitors in the tetracyclic triterpene series were synthesized, tested in vitro for the inhibition of cholinesterases (different sources of AChE and BuChE) and for the ability to prevent AChE-induced Aβ aggregation. Some compounds have hAChE IC50 values in the nanomolar range and showed ability to block the AChE-induced Aβ aggregation. The mode of interaction between EeAChE and compounds 1 and 36e was investigated using docking and molecular dynamics simulations. These studies suggested that both compounds interact simultaneously with the catalytic and the peripheral sites of AChE, and the nature of protein-ligand interactions is mainly hydrophobic. [Display omitted] ► New acetylcholinesterase inhibitors in the triterpene series were synthesized. ► Some compounds have humanAChE IC50 values in the nanomolar range. ► Some analogs showed ability to block the AChE-induced Aβ aggregation. ► A docking study and molecular dynamics simulations were done. ► These compounds interact with both catalytic and peripheral sites of AChE.