Abstract:
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder mainly characterized by progressive
deterioration of memory and impaired cognitive function. The most promising approach for symptomatic relief of AD is
to inhibit acetylcholinesterase (AChE). On the basis of this approach in-house library of 9-aminoacridine derivatives
were constructed and allowed to docked against human acetylcholinesterase (hAChE) (PDB ID: 4EY7), using MOE
2018.01 and PyRx 0.9.2 (AutoDock Vina). Top ranked and best fitted molecules were synthesized by targeting the 9-
amino group of aminoacridine with substituted phenacyl halides. Anti-Alzheimer’s potential was checked by in vitro
AChE inhibition, antioxidant activity (DPPH scavenging ability) and fibril disaggregation. Subjected ligands suggested
as promising multitargeted candidate with pronounced results in term of IC50 values (AChE inhibition 2.400-26.138µM),
however, none of them showed potential towards fibril inhibition.
