In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier.

In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from (Papaveraceae). Inhibitory activities of (+)-thalictricavine () and (+)-canadine () on human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated with the Ellman's spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of AChE. The possible permeability of and through the blood⁻brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, and were found to be selective AChE inhibitors with IC values of 0.38 ± 0.05 µM and 0.70 ± 0.07 µM, respectively, but against BChE were considered inactive (IC values > 100 µM). Furthermore, both alkaloids demonstrated a competitive-type pattern of AChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of AChE. Based on the PAMPA and logBB calculation, is potentially centrally active, but for BBB crossing is limited. In conclusion, and appear as potential lead compounds for the treatment of Alzheimer's disease.