Alzheimer, a progressive disease, is a common term for memory loss which interferes with
daily life through severe influence on cognitive abilities. Based on the cholinergic hypothesis, and Xray
crystallographic determination of the structure of acetylcholinesterase (AChE) enzyme, the level of
acetylcholine (ACh, an important neurotransmitter associated with memory) in the hippocampus and
cortex area of the brain has a direct effect on Alzheimer. This fact encourages scientists to design and
synthesize a wide range of acetylcholinesterase inhibitors (AChEIs) to control the level of ACh in the
brain, keeping in view the crystallographic structure of AChE enzyme and drugs approved by the Food
and Drug Administration (FDA).
AChEIs have slightly diverse pharmacological properties, but all of them work by inhibiting the segregation
of ACh by blocking AChE. We reviewed significant scaffolds introduced as AChEIs. In some
studies, the activity against butyrylcholinesterase (BuChE) has been evaluated as well because BuChE
is a similar enzyme to neuronal acetylcholinesterase and is capable of hydrolyzing ACh. In order to
study AChEIs effectively, we divided them structurally into 12 classes and briefly explained effective
AChEIs and compared their activities against AChE enzyme.