Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase
Abstrakt
A total of 20 derivatives (1-20) of the crinane-type alkaloid ambelline were synthesized. These semisynthetic derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).
To predict central nervous system (CNS) availability, logBB was calculated, and the data correlated well with those obtained from the parallel artificial membrane permeability assay (PAMPA). All compounds should be able to permeate the blood-brain barrier (BBB) according to the obtained results.
A total of 7 aromatic derivatives (5, 6, 7, 9, 10, 12, and 16) with different substitution patterns showed inhibitory potency against human serum BuChE (IC50 100. The in vitro results were supported by computational studies predicting plausible binding modes of the compounds in the active sites of hBuChE.