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Design, Synthesis, Molecular Docking and Biological Evaluation of Donepezil Analogues as Effective Anti-Alzheimer Agents.

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Last updated: 01 Jan 2025

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Abstract

Discovering a cure for Alzheimer's disease remains an intricate endeavor. Acetylcholinesterase enzyme (AChE) inhibitors, such as donepezil, hold a crucial position in Alzheimer's therapy. Our present study focused on the innovative design and synthesis of new analogues of donepezil, employing a click chemistry approach. We characterized the molecular structures of these synthesized compounds through a combination of elemental analysis and various spectroscopic techniques, including FT-IR, 1H NMR, and 13C NMR methods. These substances underwent assessment to determine their ability to inhibit AChE activity. Most of the tested compounds demonstrated the capacity to effectively inhibit AChE. The in vitro experiments were utilized to determine the IC50 values for the most promising candidates, which were subsequently validated using molecular docking techniques. Interestingly, compound 15 displayed the best profile with IC50 of about IC50 = 0.392 μg/mL, in addition to its high docking score (-8.86 kcal/mol) and good in silico pharmacokinetic prediction. Therefore, 15 could be a promising compound that can be used for further development of novel drugs for Alzheimer's disease.

DOI

10.21608/ejchem.2023.231046.8475

Keywords

Alzheimer's therapy, Click chemistry, Triazoles, glycosides, Acetylcholine esterase, spectroscopic techniques, pharmacokinetic prediction

Authors

First Name

Asma K.

Last Name

Alshamari

MiddleName

-

Affiliation

Department of Chemistry, College of Science, Ha'il University, Ha'il 81451, Saudi Arabia.

Email

ak.alshamari@uoh.edu.sa

City

Saudia Arabia

Orcid

-

First Name

Mohamed

Last Name

Elsawalhy

MiddleName

-

Affiliation

Department of Chemistry, Faculty of Science, Menoufia University,Shibin El-Kom 32511, Egypt.

Email

mohamed_elsawalhy22@yahoo.com

City

egypt

Orcid

-

First Name

Abdullah M.

Last Name

Alhajri

MiddleName

-

Affiliation

Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia.

Email

abdullh44.aa@gmail.com

City

Saudia Arabia

Orcid

-

First Name

Allam A.

Last Name

Hassan

MiddleName

-

Affiliation

Department of Chemistry, Faculty of Science, Suez University, Suez 43221, Egypt.

Email

allam.hassan@sci.suezuni.edu.eg

City

Cairo

Orcid

-

First Name

Mohamed G.

Last Name

Elharrif

MiddleName

-

Affiliation

Department of Basic Medical Sciences, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia

Email

al_harrif@yahoo.com

City

Saudia arabia

Orcid

-

First Name

Gigi

Last Name

Sam

MiddleName

-

Affiliation

Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia.

Email

gigisam@su.edu.sa

City

Saudi Arabia

Orcid

-

First Name

Zahra M.

Last Name

Alamshany

MiddleName

-

Affiliation

Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21551, Saudi Arabia.

Email

zalamshany@kau.edu.sa

City

Saudi Arabia

Orcid

-

First Name

Zafer S.

Last Name

Alshehri

MiddleName

-

Affiliation

Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Saudi Arabia.

Email

zaf@su.edu.sa

City

Saudi Arabia

Orcid

-

First Name

Faez F.

Last Name

Alshehri

MiddleName

-

Affiliation

Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Saudi Arabia.

Email

falshehri@su.edu.sa

City

Saudi Arabia

Orcid

-

First Name

Nasser A.

Last Name

Hassan

MiddleName

-

Affiliation

Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia., Department of Photochemistry (Synthetic Unit), Chemical Industries Research Institute, National Research Centre, Cairo 12622, Egypt

Email

nasserabdelhamid@hotmail.com

City

Cairo

Orcid

0000-0003-1809-9232

Volume

67

Article Issue

2

Related Issue

44642

Issue Date

2024-02-01

Receive Date

2023-08-22

Publish Date

2024-02-01

Page Start

473

Page End

485

Print ISSN

0449-2285

Online ISSN

2357-0245

Article File

EJCHEM_Volume 67_Issue 2_Pages 473-485.pdf

PDF . 1.3MB

Link

https://ejchem.journals.ekb.eg/article_318827.html

Detail API

https://ejchem.journals.ekb.eg/service?article_code=318827

Order

318,827

Type

Original Article

Type Code

297

Publication Type

Journal

Publication Title

Egyptian Journal of Chemistry

Publication Link

https://ejchem.journals.ekb.eg/

MainTitle

Design, Synthesis, Molecular Docking and Biological Evaluation of Donepezil Analogues as Effective Anti-Alzheimer Agents.

Details

Type

Article

Created At

30 Dec 2024