Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors

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Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors Publisher Pubmed

Ghobadian R¹ ; Esfandyari R¹ ; Nadri H² ; Moradi A² ; Mahdavi M³ ; Akbarzadeh T^{1, 4} ; Khaleghzadehahangar H⁵ ; Edraki N⁶ ; Sharifzadeh M⁷ ; Amini M¹

Show Affiliations

1. Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
2. Pharmaceutical Science Research Center and Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, 8915173143, Iran
3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
4. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
5. Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
6. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Diversity Published:2020

Abstract

Abstract: Inhibition of butyrylcholinesterase (BChE) might be a useful therapeutic target for Alzheimer’s disease (AD). A new series of 1,2,3,4-tetrahydro-9H-carbazole derivatives were designed synthesized and evaluated as BChE inhibitors. While all of the derivatives have shown for AChE IC50 values below the detectable limit (> 100 µM), they were selective potent BChE inhibitors. 1-(2-(6-fluoro-1,2,3,4-tetrahydro-9H-carbazole-9-yl)ethyl)piperidin-1-ium chloride (15 g) had the most potent anti-BChE activity (IC50 value = 0.11 μM), the highest BChE selectivity and mixed-type inhibition. Pharmacokinetic properties were accordant to Lipinski rule and compound 15g demonstrated neuroprotective and inhibition of β-secretase (BACE1) activities. Furthermore, in vivo study of compound 15g in Morris water maze task has confirmed memory improvement in scopolamine-induced impairment. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD. Graphical abstract: A new series of 1,2,3,4-tetrahydro-9H-carbazole derivatives were designed synthesized and evaluated as BChE inhibitors. While all of the derivatives have shown for AChE IC50 values below the detectable limit, they were selective potent BChE inhibitors. Compound 15g had the most potent anti-BChE activity. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD.[Figure not available: see fulltext.] © 2019, Springer Nature Switzerland AG.

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Style	Citing Format
MLA	Ghobadian R, et al.. "Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors." Molecular Diversity, vol. 24, no. 1, 2020, pp. 211-223.
APA	Ghobadian R, Esfandyari R, Nadri H, Moradi A, Mahdavi M, Akbarzadeh T, Khaleghzadehahangar H, Edraki N, Sharifzadeh M, Amini M (2020). Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors. Molecular Diversity, 24(1), 211-223.
Chicago	Ghobadian R, Esfandyari R, Nadri H, Moradi A, Mahdavi M, Akbarzadeh T, Khaleghzadehahangar H, Edraki N, Sharifzadeh M, Amini M. "Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors." Molecular Diversity 24, no. 1 (2020): 211-223.
Harvard	Ghobadian R et al. (2020) 'Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors', Molecular Diversity, 24(1), pp. 211-223.
Vancouver	Ghobadian R, Esfandyari R, Nadri H, Moradi A, Mahdavi M, Akbarzadeh T, et al.. Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors. Molecular Diversity. 2020;24(1):211-223.
BibTex	@article{ author = {Ghobadian R and Esfandyari R and Nadri H and Moradi A and Mahdavi M and Akbarzadeh T and Khaleghzadehahangar H and Edraki N and Sharifzadeh M and Amini M}, title = {Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors}, journal = {Molecular Diversity}, volume = {24}, number = {1}, pages = {211-223}, year = {2020} }
RIS	TY - JOUR AU - Ghobadian R AU - Esfandyari R AU - Nadri H AU - Moradi A AU - Mahdavi M AU - Akbarzadeh T AU - Khaleghzadehahangar H AU - Edraki N AU - Sharifzadeh M AU - Amini M TI - Design, Synthesis, in Vivo and in Vitro Studies of 1,2,3,4-Tetrahydro-9H-Carbazole Derivatives, Highly Selective and Potent Butyrylcholinesterase Inhibitors JO - Molecular Diversity VL - 24 IS - 1 SP - 211 EP - 223 PY - 2020 ER -

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