Abstract Acetylcholinesterase (AChE) is essentially a feasible target for the symptomatic improvement in Alzheimer’s disease (AD). Meanwhile, Alzheimer’s (AD) is a neurodegenerative disease which accounts for an estimated 60%–80% of dementia cases. This study investigates bioactive constituents Piper betel L as possible Acetylcholinesterase (AChE) inhibitor using pharmacophore modelling and molecular docking approach. The docking score of the analogues showed that 2-[4-(diethylamino)butyl]-5-(prop-2-en-1-yl)phenol bonded to Acetylcholinesterase (AChE) with a minimum energy of -8.4 kcal/mol and was selected as the lead molecule. The lead molecule was observed to interact with 14 amino acids within the pocket of acetylcholinesterase (AChE) and they include TRP278, ASP71, TYR120, TRP83, HIS439, GLY440, GLU198, PHE329, PHE330, TYR333, GLY 334, ILE296, PHE287 and PHE289. Meanwhile, the water solubility, druggable and pharmacokinetics index of 2-[4-(diethylamino)butyl]-5-(prop-2-en-1-yl)phenol fitted the expected druglike characteristics. Our findings showed that 2-[4-(diethylamino)butyl]-5-(prop-2-en-1-yl)phenol have good affinity for acetylcholinesterase (AChE) and can serve as therapeutics for the treatment of Alzheimer’s disease via acetylcholinesterase (AChE) inhibition.
Keywords Acetylcholinesterase (AChE), molecular docking, ADMET, Piper betel L.