Bioimpacts. 2019;9(2):79-88.
doi: 10.15171/bi.2019.11
PMID: 31334039
PMCID: PMC6637216
Scopus id: 85067466464
WOS: 000472051800002
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Original Research

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

Prayasee Baruah 1, Mostofa Ataur Rohman 1, Semen O. Yesylevskyy 2, Sivaprasad Mitra 1 * ORCiD

1 Centre for Advanced Studies in Chemistry, North-Eastern Hill University, Shillong – 793 022, India
2 Department of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Prospect Nauky 46, 03028 Kyiv, Ukraine


Introduction: Documentation on the potency of chromones as acetylcholinesterase (AChE) antagonists has paved the way for the design and usage of new chromone analogues as inhibitors of AChE modelled on the hypothesis based on cholinergic pathway of Alzheimer’s disease (AD). Here, 2 minimally substituted chromones, namely 3-cyanochromone (CyC) and 7-amino-3-methylchromone (AMC), were checked for their AChE inhibition efficacies and plasma protein modulation.
Methods: Colorimetric enzymatic assay as well as fluorescence measurements were performed for obtaining the experimental results, which were further corroborated by molecular docking and simulation studies.
Results: 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.
Conclusion: 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.
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Submitted: 21 Aug 2018
Revised: 13 Nov 2018
Accepted: 17 Nov 2018
First published online: 08 Mar 2019
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