Cholinesterase Inhibition Activity and Docking Simulation Study of Coumarin Mannich Base Derivatives

Inhibition of acetylcholinesterase and butyrylcholinesterase (ache and buche) as twomajor forms of cholinesterases (ches) is considered as the common approach for thetreatment of alzheimer's disease (ad). the present study was done to explore theanticholinesterase inhibition property of coumarin mannich base derivatives. a series ofcumarin manich bases were synthesized (4a-h) through one-pot tri-component reaction inan environmentally friendly condition and evaluated against ache and buche by ellman'sassay. ligand-protein docking simulation was also performed for the most active compound4a. additionally, the criteria of drug likeness of the target compounds was predicted usingswissadme web service. all compounds exhibited weak to moderate inhibitory activityagainst both ache and buche enzymes. compound 4a containing p-tolyl piperazin groupshowed the best activity against ache (42.4 % at 32 μm), while compound 4g bearingphenylpiperazine moiety was the best buche inhibitor (43.9% at 32 μm). ligand-proteindocking simulation also exhibited that the main part of compound 4a in che inhibitoryactivity is amine moiety. moreover, the prediction of lipinski's rule of five showed thatmost target compounds can cross the bbb and have properties that would make them likelyorally active compounds in humans. this study suggested that the synthesized cumarinmanich bases with some more structural modifications may be considered as a potentialcompound to target ache and buche.