Abstract
AbstractBackgroundInhibition of acetylcholinesterase (AChE) enzyme is considered as the most promising approach to improve the cognitive deficit complex disorders such as Alzheimer’s disease, dementia etc. The AChE also promote the aggregation of amyloid‐β complexes, mitochondrial dysfunction, a buildup of oxidative stress and neuronal cell death. Consequently, the development of compounds having polyfunctional potential could manage the complex neurodegenerative disorders like Alzheimer’s disease.MethodThe chalcone analogues were developed using bioisosteric replacement and SBDD strategies having improved therapeutic potential. The kinetics and interaction pattern with target protein of designed analogues were further evaluated using in silico methods. The leading compounds were synthesized and evaluated against AChE, AGEs formation with additional radical scavenging potential.ResultThe docking results revealed that synthesized chalcones properly fit into the active gorge of the target enzyme and displayed crucial interactions with the peripheral and catalytic sites of and having drug like properties. The in vitro assays of designed compounds against different targets showed IC50 values in nano to micro molar range.ConclusionThe dynamic simulations of the designed compounds will be carried out to evaluate the stability of the target‐ligand complex. Thus, the designed chalcones could be taken further to improve cognition deficit mainly in Alzheimer’s disease.
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