Therapeutic potency of substituted chromones as Alzheimer's drug: Elucidation of acetylcholinesterase inhibitory activity through spectroscopic and molecular modelling investigation

This comparative study affirms the importance of meticulous substitution in the chromone scaffold to promote maximum inhibition potency, while considering their usage as AD drugs.

Colorimetric enzymatic assay as well as fluorescence measurements were performed for obtaining the experimental

The investigated systems exhibited strong inhibition activities against AChE, with CyC (IC50= 85.12 ± 6.70 nM) acting as better inhibitor than AMC (IC50 = 103.09 ± 11.90 nM) and both having IC50 values in the range of FDA approved cholinergic drug Donepezil (IC50 = 74.13 ± 8.30 nM). Non-competitive inhibition was observed in both the cases with the inhibitors binding near the peripheral anionic site (PAS) of the enzyme. Having one planar nitrile group in CyC as compared to sp3 hybridised substituents in AMC facilitated stacking interactions in the former, accounting for its higher inhibitory efficacy. A significant decrease in the inhibition potency of CyC (~32%) was noted in comparison with AMC (~5%) when the experiments were performed in presence of human serum albumin (HSA) instead of pure aqueous buffer.