Pharmacokinetics, Mechanism, and Docking Study of Antioxidant Aryl-Bisthiourea Derivatives for Alzheimer's Disease

Novel aryl-bisthiourea derivatives (3 a–3 j) were synthesized by a two-step route for the study of free-radical scavenging property and acetylcholinesterase enzyme (AChE) inhibition study. The effect of the electronic environment on the aryl structure of ArBTU on the AChE inhibition was studied. Lineweaver-Burk plot was used for kinetic study of inhibition of AChE by using ArBTU derivatives which exhibited very good bioactivity of inhibition against acetylcholinesterase enzyme. Central Nervous System (CNS) permeability and the Blood-Brain Barrier values of all ArBTU derivatives (3 a–3 j) were also similar to the reference value (>−2 logPS< −3 and >−0.3 log BB< −1), respectively. The molecular docking study of derivative 3 g presented a very good interactions with tested protein. The mechanism of AChE inhibition was found from the kinetic studies of novel ArBTU derivatives. A pharmacokinetic study of AChE inhibition was also evaluated. ArBTU derivatives (3 a–3 j) exhibited the best lead-like potential. Molecular docking study described the binding ability of the highly effective derivative 3 g with the acetylcholinesterase enzyme.