Galantamine derivatives as acetylcholinesterase inhibitors: Docking, design, synthesis, and inhibitory activity

Abstract

Galantamine (GAL) is a well-known acetylcholinesterase (AChE) inhibitor, and it is widely used for treatment of Alzheimer’s disease. GAL fits well in the catalytic site of AChE, but it is too short to block the peripheral anionic site (PAS) of the enzyme, where the amyloid beta (Aβ) peptide binds and initiates the Aβ aggregation. Here, we describe a docking-based technique for designing of GAL derivatives with dual-site binding fragments – one blocking the catalytic site and another blocking the PAS. The highly scored compounds are synthesized and tested. Protocols for docking, design, synthesis, and AChE inhibitory test are given.