Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations

Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations Publisher

Zareei S¹ ; Mohammadikhanaposhtani M² ; Shahali M³ ; Senol H⁴ ; Badbedast M⁵ ; Moazzam A¹ ; Mohseni S¹ ; Esfahani EN⁶ ; Ekti SF⁷ ; Larijani B¹ ; Mahdavi M¹ ; Ibrahim EH^{8, 9, 10} ; Ghramh HA^{8, 9, 11} ; Taslimi P¹²

Show Affiliations

1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
3. School of pharmacy, Tehran university of medical sciences, Tehran, Iran
4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, Fatih Istanbul, 34093, Turkey
5. School of Chemistry, College of Science, University of Tehran, Tehran, Iran
6. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran, University of Medical Sciences, Tehran, Iran
7. Department of Chemistry, Eskisehir Technical University, Faculty of Science, Eskisehir, 26555, Turkey
8. Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
9. Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
10. Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, Egypt
11. Unit of Bee Research and Honey Production, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
12. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, 74100, Turkey

Source: Journal of Molecular Structure Published:2025

Abstract

In this work, phenyldiazenyl-phenoxy-1,2,3-triazol-acetamide as new scaffold was designed by molecular hybridization of the active pharmacophores in the cholinesterase inhibitors. Twelve derivatives 7a-l of the title scaffold were synthesized in high yields using simple and efficient chemical reactions. The inhibitory activities of all the title compounds 7a-l were investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as two important enzymatic targets in Alzheimer's disease (AD). The obtained in vitro data showed that all new compounds were more potent than positive control galantamine against both studied enzymes. Representatively, the most potent compound against AChE (compound 7 g) was 2.7-times and the most potent compound against BChE (compound 7k) was 40.5-times more potent than galantamine. Docking study demonstrated that the most potent compounds interacted with main components of the active sites of AChE and BChE. Molecular dynamics of the most potent compounds showed that these compounds formed stable complex with target enzymes AChE and BChE. The most potent compounds also had acceptable pharmacokinetic properties as oral agents. © 2024 Elsevier B.V.

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Style	Citing Format
MLA	Zareei S, et al.. "Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations." Journal of Molecular Structure, vol. 1321, no. , 2025, pp. -.
APA	Zareei S, Mohammadikhanaposhtani M, Shahali M, Senol H, Badbedast M, Moazzam A, Mohseni S, Esfahani EN, Ekti SF, Larijani B, Mahdavi M, Ibrahim EH, Ghramh HA, Taslimi P (2025). Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations. Journal of Molecular Structure, 1321(), -.
Chicago	Zareei S, Mohammadikhanaposhtani M, Shahali M, Senol H, Badbedast M, Moazzam A, Mohseni S, et al.. "Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations." Journal of Molecular Structure 1321, no. (2025): -.
Harvard	Zareei S et al. (2025) 'Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations', Journal of Molecular Structure, 1321(), pp. -.
Vancouver	Zareei S, Mohammadikhanaposhtani M, Shahali M, Senol H, Badbedast M, Moazzam A, et al.. Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations. Journal of Molecular Structure. 2025;1321():-.
BibTex	@article{ author = {Zareei S and Mohammadikhanaposhtani M and Shahali M and Senol H and Badbedast M and Moazzam A and Mohseni S and Esfahani EN and Ekti SF and Larijani B and Mahdavi M and Ibrahim EH and Ghramh HA and Taslimi P}, title = {Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations}, journal = {Journal of Molecular Structure}, volume = {1321}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Zareei S AU - Mohammadikhanaposhtani M AU - Shahali M AU - Senol H AU - Badbedast M AU - Moazzam A AU - Mohseni S AU - Esfahani EN AU - Ekti SF AU - Larijani B AU - Mahdavi M AU - Ibrahim EH AU - Ghramh HA AU - Taslimi P TI - Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations JO - Journal of Molecular Structure VL - 1321 IS - SP - EP - PY - 2025 ER -

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