Theoretical examination of molecular docking, pharmacokinetics and in-silico design of specific tacrine derivatives as anti-Alzheimer agents

Abstract

A common neurological illness that affects many individuals globally is Alzheimer's disease (AD). Its cause is currently unknown. One of the symptoms of AD is a reduction in cholinergic transmission, which has been linked to memory loss and cognitive impairment. Acetylcholinesterase (AChE) inhibitors such as donepezil, galantamine, and rivastigmine are used in medicine. However, their unfavourable side effects have caused them to be taken off the market. Because tacrine inhibits the enzyme AChE, molecular docking modelling has been used to simulate and create a variety of derivatives. The purpose of this work was to develop some strong Alzheimer's inhibitors and to calculate the binding scores of tacrine derivatives theoretically. Following docking, molecule A8 was selected as a template for creating new compounds since it had the greatest binding scores (-9.8 kcal/mol). The B3, B5, B6, B8, and B10 hypothetical molecules were constructed. The developed compounds' ADMET prediction and drug-likeness demonstrate strong pharmacokinetic properties. Furthermore, comparable strong inhibitor drugs against AD might be created using the in-silico methodologies used in this work.