Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents

Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents Publisher Pubmed

Shamsimeymandi R¹ ; Pourshojaei Y^{1, 2} ; Eskandari K¹ ; Mohammadikhanaposhtani M³ ; Abiri A¹ ; Khodadadi A¹ ; Langarizadeh A¹ ; Sharififar F⁴ ; Amirheidari B⁵ ; Akbarzadeh T^{6, 7} ; Lotfian H⁷ ; Foroumadi A^{2, 8} ; Asadipour A¹

Show Affiliations

1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran
2. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4. Department of Pharmacognosy, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
6. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
8. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Archiv der Pharmazie Published:2019

Abstract

A series of novel chroman-4-one derivatives were designed and synthesized successfully with good to excellent yield (3a–l). In addition, the obtained products were evaluated for their cholinesterase (ChE) inhibitory activities. The results show that among the various synthesized compounds, analogs bearing the piperidinyl ethoxy side chain with 4-hydroxybenzylidene on the 3-positions of chroman-4-one (3l) showed the most potent activity with respect to acetylcholinesterase (anti-AChE activity; IC50 = 1.18 μM). In addition, the structure–activity relationship was studied and the results revealed that the electron-donating groups on the aryl ring of the 3-benzylidene fragment (3k, 3l) resulted in the designed compounds to be more potent ChE inhibitors in comparison with those having electron-withdrawing groups (3h). In this category, the strongest ChE inhibition was found for the compound containing piperidine as cyclic amine, and a hydroxyl group (for AChE, compound 3l) and fluoro group (for butyrylcholinesterase (BuChE, compound 3i) on the para-position of the aryl ring of the benzylidene group. The molecular docking and dynamics studies of the most potent compounds (3i and 3l against BuChE and AChE, respectively) demonstrated remarkable interactions with the binding pockets of the ChE enzymes and confirmed the results obtained through in vitro experiments. © 2019 Deutsche Pharmazeutische Gesellschaft

Style	Citing Format
MLA	Shamsimeymandi R, et al.. "Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents." Archiv der Pharmazie, vol. 352, no. 7, 2019, pp. -.
APA	Shamsimeymandi R, Pourshojaei Y, Eskandari K, Mohammadikhanaposhtani M, Abiri A, Khodadadi A, Langarizadeh A, Sharififar F, Amirheidari B, Akbarzadeh T, Lotfian H, Foroumadi A, Asadipour A (2019). Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents. Archiv der Pharmazie, 352(7), -.
Chicago	Shamsimeymandi R, Pourshojaei Y, Eskandari K, Mohammadikhanaposhtani M, Abiri A, Khodadadi A, Langarizadeh A, et al.. "Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents." Archiv der Pharmazie 352, no. 7 (2019): -.
Harvard	Shamsimeymandi R et al. (2019) 'Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents', Archiv der Pharmazie, 352(7), pp. -.
Vancouver	Shamsimeymandi R, Pourshojaei Y, Eskandari K, Mohammadikhanaposhtani M, Abiri A, Khodadadi A, et al.. Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents. Archiv der Pharmazie. 2019;352(7):-.
BibTex	@article{ author = {Shamsimeymandi R and Pourshojaei Y and Eskandari K and Mohammadikhanaposhtani M and Abiri A and Khodadadi A and Langarizadeh A and Sharififar F and Amirheidari B and Akbarzadeh T and Lotfian H and Foroumadi A and Asadipour A}, title = {Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents}, journal = {Archiv der Pharmazie}, volume = {352}, number = {7}, pages = {-}, year = {2019} }
RIS	TY - JOUR AU - Shamsimeymandi R AU - Pourshojaei Y AU - Eskandari K AU - Mohammadikhanaposhtani M AU - Abiri A AU - Khodadadi A AU - Langarizadeh A AU - Sharififar F AU - Amirheidari B AU - Akbarzadeh T AU - Lotfian H AU - Foroumadi A AU - Asadipour A TI - Design, Synthesis, Biological Evaluation, and Molecular Dynamics of Novel Cholinesterase Inhibitors As Anti-Alzheimer's Agents JO - Archiv der Pharmazie VL - 352 IS - 7 SP - EP - PY - 2019 ER -

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