Insilico Analysis and Docking of Tacrine and Donepezil Derivatives Targeting Histamine-N-Methyltransferase and Acetyl Cholinesterase Protein Respectively for Alzheimer's Disease

Alzheimer's disease is characterized by loss of neurons and synapses in the cerebral cortex and certain sub cortical regions. The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. As the disease advances, symptoms include confusion, irritability and aggression, long-term memory loss. Two drugs specifically approved for treating Alzheimer's disease were Tacrine and Donezepil. Tacrine mainly inhibit the histamine-N-methyltransferase protein which block the histamine transmission. Donepezil inhibit the acetyl cholinesterase which degrades the acetylcholine transmitter. In this study, computational methods are used to design novel tacrine and donepezil derivatives and evaluated them for interaction with the Histamine-N-methyltransferase protein and acetyl cholinesterase protein respectively through insilico analysis by using Hyperchem 8.0, Gold 3.01 docking software. The result of the docking studies shows that ligands of T₃ and D₃ with R -CH₂CH₃ are having highest binding affinity.