Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations

Yossra A. Malik; Talal Ahmed Awad; Mohnad Abdalla; Sakina Yagi; Hassan A. Alhazmi; Waquar Ahsan; Mohammed Albratty; Asim Najmi; Shabbir Muhammad; Asaad Khalid

doi:10.3390/molecules27103181

Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations

Yossra A. Malik, Talal Ahmed Awad, Mohnad Abdalla, Sakina Yagi, Hassan A. Alhazmi, Waquar Ahsan, Mohammed Albratty, Asim Najmi, Shabbir Muhammad, Asaad Khalid

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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)
Pages (from-to)	3181
Journal	Molecules (Basel, Switzerland)
Volume	27
Issue number	10
DOIs	https://doi.org/10.3390/molecules27103181
State	Published - May 1 2022
Externally published	Yes

Bibliographical note

KAUST 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

Access to Document

10.3390/molecules27103181

Cite this

@article{a4c6efc52099415e8110ba4403f8ecf5,

title = "Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations",

abstract = "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.",

author = "Malik, {Yossra A.} and Awad, {Talal Ahmed} and Mohnad Abdalla and Sakina Yagi and Alhazmi, {Hassan A.} and Waquar Ahsan and Mohammed Albratty and Asim Najmi and Shabbir Muhammad and Asaad Khalid",

note = "KAUST 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.",

year = "2022",

month = may,

day = "1",

doi = "10.3390/molecules27103181",

language = "English (US)",

volume = "27",

pages = "3181",

journal = "Molecules (Basel, Switzerland)",

issn = "1420-3049",

publisher = "MDPI",

number = "10",

}

TY - JOUR

T1 - Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations

AU - Malik, Yossra A.

AU - Awad, Talal Ahmed

AU - Abdalla, Mohnad

AU - Yagi, Sakina

AU - Alhazmi, Hassan A.

AU - Ahsan, Waquar

AU - Albratty, Mohammed

AU - Najmi, Asim

AU - Muhammad, Shabbir

AU - Khalid, Asaad

N1 - KAUST 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.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/678357

UR - https://www.mdpi.com/1420-3049/27/10/3181

U2 - 10.3390/molecules27103181

DO - 10.3390/molecules27103181

M3 - Article

C2 - 35630658

SN - 1420-3049

VL - 27

SP - 3181

JO - Molecules (Basel, Switzerland)

JF - Molecules (Basel, Switzerland)

IS - 10

ER -

Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this