Flavonols and 4-Thioflavonols as Potential Acetylcholinesterase and Butyrylcholinesterase Inhibitors: Synthesis, Structure-Activity Relationship and Molecular Docking Studies

Abstract To explore new scaffolds for the treat of Alzheimer’s disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1 H-, 13 C-NMR) and mass spectrometry (EI-MS). All the derivatives ( 1-24 ) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC 50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC 50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.