Novel Acetylcholinesterase Inhibitors Identified from ZINC Database Using Docking-Based Virtual Screening for Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease related to ageing. Cholinesterases are a family of enzymes that catalyse the hydrolysis of acetylcholine (ACh), which is an essential process in the cholinergic neurotransmission. Cholinesterases can be divided into two types, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This paper reports virtual screening and molecular docking of 200 compounds obtained from the ZINC database, using AutoDock Vina and AutoDock 4.2 to find potential AChE inhibitors. Only compounds that are compliant with Lipinski's rule of five for drug-likeness properties were virtually screened to identify novel compounds that show similar or better interaction with the target protein compared to the coordinated ligand galantamine. The results showed that 6 compounds, namely ZINC10140364, ZINC08061148, ZINC34735322, ZINC05151975, ZINC33126088 and ZINC15805418, exhibited better free energy of binding (FEB) than galantamine, with AutoDock Vina scores of -9.88, -10.44, -10.30, -9.63, -8.35 and -9.42 kcal/mol and AutoDock scores of -12.3, -11.6, -11.0, -10.9, -10.5 and -9.3 kcal/mol, respectively. In conclusion, the results obtained suggest that the 6 compounds are potential AChE inhibitors suitable for further evaluation and development as potential agents for treatment.