6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study

6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study Publisher

Chehardoli G¹ ; Gholamhoseini P² ; Ebadi A¹ ; Ziaei M² ; Akbarzadeh T^{3, 4} ; Saeedi M^{4, 5} ; Mahdavi M⁶ ; Khoshneviszadeh M⁷ ; Najafi Z²

Show Affiliations

1. Department of Medicinal Chemistry, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 6517838678, Iran
2. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 6517838678, Iran
3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar Street, Tehran, 1417614411, Iran
4. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, 16 Azar Street, Tehran, 1417614411, Iran
5. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 16 Azar Street, Tehran, 1417614411, Iran
6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, 1411713137, Iran
7. Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, 7146864685, Iran

Source: ChemistrySelect Published:2022

Abstract

A novel series of 6-methoxy-1-tetralone derivatives bearing N-aryl pyridinium moiety were designed, synthesized, and evaluated as acetyl and butyrylcholinesterase inhibitors. The designed derivatives inhibited acetylcholinesterase (AChE) with IC50 values of 0.025–23.743 μM and butyrylcholinesterase (BChE) with IC50 values of 0.716–20.588 μM. The synthesized compounds were divided into two series. Derivatives containing N-benzyl moieties generally were more potent anti-AChE and anti-BChE agents than compounds with N-alkylphthalimide groups. Among them, the compound (E)-1-Benzyl-3-((6-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)methyl)pyridin-1-ium bromide (5 a) and compound (E)-1-(3-Chlorobenzyl)-3-((6-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)methyl)pyridin-1-ium bromide (5 d) exhibited significant inhibitory activity against AChE and BChE with IC50 values of 0.025 and 0.716 μM in comparison to donepezil as a reference drug (0.029 and 0.948 μM, respectively). The results of kinetic and molecular modeling studies demonstrated that the synthesized compounds 5 a and 5 d derivatives can act as mixed and dual binding inhibitors, and bind to both CAS and PAS of AChE and BChE enzymes. Among the assessed compounds, the compound 5 a indicated significant neuroprotection against H2O2-induced cell death in PC12 cells. So, these findings indicate the therapeutic potential of 6-methoxy-1-tetralone derivatives bearing N-aryl pyridinium moiety derivatives as anti-AD agents. © 2022 Wiley-VCH GmbH.

Style	Citing Format
MLA	Chehardoli G, et al.. "6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study." ChemistrySelect, vol. 7, no. 27, 2022, pp. -.
APA	Chehardoli G, Gholamhoseini P, Ebadi A, Ziaei M, Akbarzadeh T, Saeedi M, Mahdavi M, Khoshneviszadeh M, Najafi Z (2022). 6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study. ChemistrySelect, 7(27), -.
Chicago	Chehardoli G, Gholamhoseini P, Ebadi A, Ziaei M, Akbarzadeh T, Saeedi M, Mahdavi M, Khoshneviszadeh M, Najafi Z. "6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study." ChemistrySelect 7, no. 27 (2022): -.
Harvard	Chehardoli G et al. (2022) '6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study', ChemistrySelect, 7(27), pp. -.
Vancouver	Chehardoli G, Gholamhoseini P, Ebadi A, Ziaei M, Akbarzadeh T, Saeedi M, et al.. 6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study. ChemistrySelect. 2022;7(27):-.
BibTex	@article{ author = {Chehardoli G and Gholamhoseini P and Ebadi A and Ziaei M and Akbarzadeh T and Saeedi M and Mahdavi M and Khoshneviszadeh M and Najafi Z}, title = {6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study}, journal = {ChemistrySelect}, volume = {7}, number = {27}, pages = {-}, year = {2022} }
RIS	TY - JOUR AU - Chehardoli G AU - Gholamhoseini P AU - Ebadi A AU - Ziaei M AU - Akbarzadeh T AU - Saeedi M AU - Mahdavi M AU - Khoshneviszadeh M AU - Najafi Z TI - 6-Methoxy-1-Tetralone Derivatives Bearing an N-Arylpyridinium Moiety As Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Molecular Docking Study JO - ChemistrySelect VL - 7 IS - 27 SP - EP - PY - 2022 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract