Anti-Acetylcholinesterase Derivatives: A Privileged Structural Framework in Drug Discovery to Treat Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurological disorder characterised by decrease level of ACh and increased AChE expression. Inhibition of AChE is one of the common strategies to treat AD as it leads to increase Ach level quantitatively at the synaptic cleft. Acetylcholinesterase inhibitors (AChEIs) are used to treat various neurodegenerative disorders, and many are FDA approved for the management and cure of AD. AChEIs produce long term symptomatic effect, that contribute in other pathological mechanisms of the disease (e.g. formation of amyloid–β plaques) and have provided a rationale to the discovery of this class of inhibitors. Currently prescribed AChE inhibitors are Galantamine (natural alkaloid) and Rivastigmine (synthetic alkaloid compound) and have been considered beneficial for the treatment of mild to moderate AD. However, there is a need for the discovery of more effective compounds derived from natural sources as well as form synthetic sources as potential AChEIs. Findings and advances about natural and synthetic derivatives as potential sources of AChEIs will be collectively summarised in this review paper.