Rouleau_2011_Eur.J.Med.Chem_46_2193

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 Abeta aggregation. Some compounds have hAChE IC50 values in the nanomolar range and showed ability to block the AChE-induced Abeta 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.