Insilico Design and Discovery of Some Novel Ache Inhibitors for Treatment of Alzheimer's Disorder

Enzyme Acetyl cholinesterase (AChE) catalyzes the neurotransmitter acetylcholine (ACh) at synaptic clefts of the neurons. Apart from its hydrolyzing activity it is also known to play an important role in amyloid formation thus causing Alzheimer’s disease (AD). AD is associated with significant loss of cholinergic neurons and reduced levels of ACh, which significantly impairs learning and memory processes. Acetyl cholinesterase inhibitors (ACIs) are one of the widely used drugsfor the treatment of mild to moderate Alzheimer’s dementia. Acetyl cholinesteraseinhibitors improve the neurological behavior by increasing availability of acetylcholine at synapse in the presence of intact cholinergic neurons. So identifying potent AChE inhibitors may declineneuro degeneration in AD patients. In this computational study, several novel AChE inhibitors were designed and optimized in the software Hyperchem. Also, these inhibitors were docked with the AChE in FLExX docking program and toxicity studies were conducted using OSIRIS property explorer. Here, the ligand 15 has shown better interaction and high binding affinity with AChE.