This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1–C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand–protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 μM) in correlation with the in silico results (binding energies = −8.55 to −8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π–π, π–cation, π–sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.
|Original language||English (US)|
|Journal||Molecules (Basel, Switzerland)|
|State||Published - May 1 2022|
Bibliographical noteKAUST Repository Item: Exported on 2022-06-01
Acknowledgements: The author (S.M.) from King Khalid University of Saudi Arabia wishes to extend his appreciation to the Deanship of Scientific Research, King Khalid University for supporting the work (RGP.2/194/43). For computer time, this research used the resources of the supercomputing laboratory at King Abdullah University of Science and Technology (KAUST) in Thuwal, Saudi Arabia.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.
ASJC Scopus subject areas
- Organic Chemistry