In-Silico Design, Molecular Docking and Pharmacokinetics Studies of Some Tacrine Derivatives as Anti-Alzheimer Agents: Theoretical Investigation

Alzheimer's disease (AD) is a neurodegenerative ailment that affects many people worldwide. Its cause has yet to be determined. One of the symptoms of AD is the loss of cholinergic transmission, which is related to cognitive impairment and memory loss. Acetylcholinesterase (AChE) inhibitors like donepezil, galantamine, and rivastigmine are currently used in medicine, but they have been taken off the market due to their adverse side effects. Molecular docking simulation was used to simulate and design some tacrine derivatives because of the inhibitory ability of tacrine on the enzyme AChE. This study was tailored to theoretically calculate the tacrine derivatives binding scores and design some potent Alzheimer's inhibitors. After docking, molecule A۸ has the highest binding scores of -۹.۸ kcal/mol, and it was chosen as a template for designing new compounds. Five new hypothetical molecules (B۳, B۵, B۶, B۸, and B۱۰) were designed. ADMET prediction of the designed molecules and drug-likeness show good pharmacokinetic abilities. Moreover, the in-silico techniques used in this study could further design similar potent inhibitor compounds against AD.

کلیدواژه ها:

Design compounds ، Binding score ، Alzheimer's disease ، pharmacokinetics ، Molecular docking