Design of new Rivastigmine analogs based on Molecular Docking and Binding Free Energy calculations

Alzheimer’s disease (AD) is a relative lack of brain chemical neurotransmitter, Acetylcholine. Dementia is a progressive, degenerative brain disease affecting memory, thinking and behavior due to increase in the accumulation of specific protein, beta-amyloid protein in the brain that leads to nerve cell death. Acetyl cholinesterase (Ach E) is an essential enzyme for metabolism of acetylcholine. The cholinesterase inhibitors, like rivastigmine block the breakdown of acetylcholine. The present paper describes the molecular docking studies of novel drug rivastigmine which inhibits the activity of acetyl cholinesterase to slow the progression of AD and possibly improve the person’s mental capabilities. Docking studies of rivastigmine have been carried out in the active site using GOLD software. Main objective is to study the effectiveness of rivastigmine and its analogs for the treatment of Alzheimer’s disease targeting acetyl cholinesterase with molecular docking studies and Binding free energy calculations using GOLD HYPERCHEM and OPENEYE SOFTWARE. Of the six analogs for Alzheimer’s disease, from the molecular docking studies it was found analog 2 with substitution NHOH was the most effective analog in inhibiting the activity of acetyl cholinesterase.