Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors

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Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors Publisher Pubmed

Ghobadian R¹ ; Nadri H² ; Moradi A² ; Bukhari SNA³ ; Mahdavi M⁴ ; Asadi M¹ ; Akbarzadeh T^{1, 5} ; Khaleghzadehahangar H⁶ ; Sharifzadeh M⁷ ; Amini M¹

Source: Bioorganic and Medicinal Chemistry Published:2018

Abstract

Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl Pyridine derivatives were designed synthesized and evaluated as butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9-yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most potent anti-BChE activity (IC 50 value = 0.073 μM), the highest BChE selectivity and mixed-type inhibition. Docking study revealed that 8f interacted with the peripheral site, the choline binding site, catalytic site and the acyl pocket of BChE. Physicochemical properties were accurate to Lipinski's rule. In addition, compound 8f demonstrated neuroprotective activity at 10 µM. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100 µM and 10 µM respectively. The in-vivo study showed that compound 8f in 10 mg/kg increased the time spent in target quadrant in the probe day and decreased mean training period scape latency in rats. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD. © 2018 Elsevier Ltd

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Style	Citing Format
MLA	Ghobadian R, et al.. "Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors." Bioorganic and Medicinal Chemistry, vol. 26, no. 17, 2018, pp. 4952-4962.
APA	Ghobadian R, Nadri H, Moradi A, Bukhari SNA, Mahdavi M, Asadi M, Akbarzadeh T, Khaleghzadehahangar H, Sharifzadeh M, Amini M (2018). Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors. Bioorganic and Medicinal Chemistry, 26(17), 4952-4962.
Chicago	Ghobadian R, Nadri H, Moradi A, Bukhari SNA, Mahdavi M, Asadi M, Akbarzadeh T, Khaleghzadehahangar H, Sharifzadeh M, Amini M. "Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors." Bioorganic and Medicinal Chemistry 26, no. 17 (2018): 4952-4962.
Harvard	Ghobadian R et al. (2018) 'Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors', Bioorganic and Medicinal Chemistry, 26(17), pp. 4952-4962.
Vancouver	Ghobadian R, Nadri H, Moradi A, Bukhari SNA, Mahdavi M, Asadi M, et al.. Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors. Bioorganic and Medicinal Chemistry. 2018;26(17):4952-4962.
BibTex	@article{ author = {Ghobadian R and Nadri H and Moradi A and Bukhari SNA and Mahdavi M and Asadi M and Akbarzadeh T and Khaleghzadehahangar H and Sharifzadeh M and Amini M}, title = {Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors}, journal = {Bioorganic and Medicinal Chemistry}, volume = {26}, number = {17}, pages = {4952-4962}, year = {2018} }
RIS	TY - JOUR AU - Ghobadian R AU - Nadri H AU - Moradi A AU - Bukhari SNA AU - Mahdavi M AU - Asadi M AU - Akbarzadeh T AU - Khaleghzadehahangar H AU - Sharifzadeh M AU - Amini M TI - Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors JO - Bioorganic and Medicinal Chemistry VL - 26 IS - 17 SP - 4952 EP - 4962 PY - 2018 ER -

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