title: New potent human acetylcholinesterase inhibitors in the tetracyclic triterpene series with inhibitory potency on amyloid β aggregation.
abstract: 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.
authors: Institut de Chimie des Substances Naturelles, Bt 27, CNRS Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors: Julien
authors: J
authors: Rouleau
authors: Bogdan I
authors: BI
authors: Iorga
authors: Catherine
authors: C
authors: Guillou
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D014315:Triterpenes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase