Comparison of In Silico AChE Inhibitory Potentials of Some Donepezil Analogues

Abstract

Cholinesterases are important in ensuring hemostasis in our body. Excessive increase in cholinesterase function causes various cholinergic dysfunctions. Alzheimer's is a disease characterized by loss of cholinergic activity, which is especially common in the elderly. One of the cholinesterase inhibitors most commonly used to stop the progression of Alzheimer's disease is donepezil. Due to some side effects of donepezil, the synthesis and design of new analogues that may be alternatives to donepezil are reported in the literature. In this study, molecular docking studies were performed to compare the in silico AChE inhibitory potential of some new structural analogs of donepezil. Molecular docking studies were performed using Autodock4.2 tools. In this study, the hypothesis emerges that especially compound 1 and compound 5 have the potential to inhibit AChE at least as much as donepezil. In silico docking studies showed that donepezil derivatives designed with bioisosteres of the piperidine ring in donepezil have high binding affinity towards acetylcholine esterase. These results need to be confirmed by synthesis of the donepezil analogues designed in the study and in vitro activity measurements.

Keywords

• Acetylcholinesterase Inhibitor
• bioisostere
• donepezil
• Molecular Docking Simulations
• piperidine

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