Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Novel Coumarin–Pyridine Hybrids As Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer’S Disease Publisher



Babaei E1 ; Kucukkilinc TT2 ; Jalilibaleh L3 ; Nadri H4 ; Oz E2 ; Forootanfar H5 ; Hosseinzadeh E6 ; Akbari T7 ; Ardestani MS8 ; Firoozpour L3 ; Foroumadi A3 ; Sharifzadeh M9 ; Mirjalili BBF1 ; Khoobi M6, 8
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran
  2. 2. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran University of Medical Science, Tehran, Iran
  4. 4. Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  5. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  6. 6. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran
  8. 8. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Frontiers in Chemistry Published:2022


Abstract

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2–144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9–123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce β-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD. Copyright © 2022 Babaei, Kucukkilinc, Jalili-Baleh, Nadri, Oz, Forootanfar, Hosseinzadeh, Akbari, Ardestani, Firoozpour, Foroumadi, Sharifzadeh, Mirjalili and Khoobi.
Related Docs
View other Related Docs
1. 3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Chemistry and Biodiversity (2019)
2. Novel 3-Phenylcoumarin–Lipoic Acid Conjugates As Multi-Functional Agents for Potential Treatment of Alzheimer's Disease, Bioorganic Chemistry (2018)
3. Synthesis and Biological Evaluation of New N-Benzylpyridinium-Based Benzoheterocycles As Potential Anti-Alzheimer's Agents, Bioorganic Chemistry (2019)
4. Chromone Derivatives Bearing Pyridinium Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Bioorganic Chemistry (2021)
5. Design, Synthesis and Evaluation of Novel Multi-Target-Directed Ligands for Treatment of Alzheimer's Disease Based on Coumarin and Lipoic Acid Scaffolds, European Journal of Medicinal Chemistry (2018)
6. New Benzyl Pyridinium Derivatives Bearing 2,4-Dioxochroman Moiety As Potent Agents for Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and Docking Study, Bioorganic Chemistry (2019)
7. Novel 3-Aminobenzofuran Derivatives As Multifunctional Agents for the Treatment of Alzheimer’S Disease, Frontiers in Chemistry (2022)
8. Chromone–Lipoic Acid Conjugate: Neuroprotective Agent Having Acceptable Butyrylcholinesterase Inhibition, Antioxidant and Copper-Chelation Activities, DARU# Journal of Pharmaceutical Sciences (2021)
Experts (# of related papers)
View all Related Experts
Mohammad Mahdavi (29)
Alireza Foroumadi (23)
Other Related Docs
9. New Classes of Carbazoles As Potential Multi-Functional Anti-Alzheimer's Agents, Bioorganic Chemistry (2019)
10. Novel Tacrine-Coumarin Hybrids Linked to 1,2,3-Triazole As Anti-Alzheimer's Compounds: In Vitro and in Vivo Biological Evaluation and Docking Study, Bioorganic Chemistry (2019)
11. Synthesis of New 3-Arylcoumarins Bearing N-Benzyl Triazole Moiety: Dual Lipoxygenase and Butyrylcholinesterase Inhibitors With Anti-Amyloid Aggregation and Neuroprotective Properties Against Alzheimer’S Disease, Frontiers in Chemistry (2022)
12. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents, Chemistry and Biodiversity (2019)
13. Design and Synthesis of Benzodiazepine-1,2,3-Triazole Hybrid Derivatives As Selective Butyrylcholinesterase Inhibitors, Molecular Diversity (2020)
14. Synthesis of Novel Chromenones Linked to 1,2,3-Triazole Ring System: Investigation of Biological Activities Against Alzheimer's Disease, Bioorganic Chemistry (2017)
15. Synthesis and Cholinesterase Inhibitory Activity of New 2-Benzofuran Carboxamide-Benzylpyridinum Salts, Bioorganic Chemistry (2018)
16. Design and Synthesis of Multi-Target Directed 1,2,3-Triazole-Dimethylaminoacryloyl-Chromenone Derivatives With Potential Use in Alzheimer's Disease, BMC Chemistry (2020)
17. Synthesis of Novel 1,2,3-Triazole-Dihydro[3,2-C[Chromenones As Acetylcholinesterase Inhibitors, Synthetic Communications (2015)
18. Coumarin-Based Scaffold As Α-Glucosidase Inhibitory Activity: Implication for the Development of Potent Antidiabetic Agents, Mini-Reviews in Medicinal Chemistry (2020)
19. Synthesis, Docking Study, and Biological Evaluation of Novel Umbellipherone/Hymecromone Derivatives As Acetylcholinesterase/Butyrylcholinesterase Inhibitors, Medicinal Chemistry Research (2018)
20. New Racemic Annulated Pyrazolo[1,2-B]Phthalazines As Tacrine-Like Ache Inhibitors With Potential Use in Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)
21. Design, Synthesis, and Cholinesterase Inhibition Assay of Coumarin-3-Carboxamide-N-Morpholine Hybrids As New Anti-Alzheimer Agents, Chemistry and Biodiversity (2019)
22. Synthesis and Antiacetylcholinesterase Activity Evaluation of New 2-Aryl Benzofuran Derivatives, Letters in Drug Design and Discovery (2016)
23. A Review on Tacrine-Based Scaffolds As Multi-Target Drugs (Mtdls) for Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)
24. Design and Synthesis of Novel Arylisoxazole-Chromenone Carboxamides: Investigation of Biological Activities Associated With Alzheimer's Disease, Chemistry and Biodiversity (2020)
25. Cholinesterase Inhibition Activity and Docking Simulation Study of Coumarin Mannich Base Derivatives, Journal of Sciences# Islamic Republic of Iran (2019)
26. Synthesis and Evaluation of Coumarin-Resveratrol Hybrids As 15-Lipoxygenaze Inhibitors, Synthetic Communications (2015)
27. Synthesis and in Vitro Biological Activity Evaluation of Novel Imidazo [2,1-B][1,3,4] Thiadiazole As Anti-Alzheimer Agents, Letters in Drug Design and Discovery (2020)
28. Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole-Phenylpiperazine Derivatives, Chemistry and Biodiversity (2019)
29. Design, Synthesis, Molecular Docking, and Cholinesterase Inhibitory Potential of Phthalimide-Dithiocarbamate Hybrids As New Agents for Treatment of Alzheimer's Disease, Chemistry and Biodiversity (2019)
30. Satureja Bachtiarica Ameliorate Beta-Amyloid Induced Memory Impairment, Oxidative Stress and Cholinergic Deficit in Animal Model of Alzheimer’S Disease, Metabolic Brain Disease (2016)
31. Novel Tetrahydrocarbazole Benzyl Pyridine Hybrids As Potent and Selective Butryl Cholinesterase Inhibitors With Neuroprotective and Β-Secretase Inhibition Activities, European Journal of Medicinal Chemistry (2018)
32. Design and Synthesis of Novel Anti-Alzheimer's Agents: Acridine-Chromenone and Quinoline-Chromenone Hybrids, Bioorganic Chemistry (2016)
33. Design, Synthesis and Anti-Alzheimer's Activity of Novel 1,2,3-Triazole-Chromenone Carboxamide Derivatives, Bioorganic Chemistry (2019)
34. Hetero-Annulated Coumarins As New Ache/Buche Inhibitors: Synthesis and Biological Evaluation, Medicinal Chemistry Research (2016)
35. Recent Developments in the Design and Synthesis of Benzylpyridinium Salts: Mimicking Donepezil Hydrochloride in the Treatment of Alzheimer’S Disease, Frontiers in Chemistry (2022)
36. Design, Synthesis, Molecular Modeling and Anticholinesterase Activity of Benzylidene-Benzofuran-3-Ones Containing Cyclic Amine Side Chain, Future Medicinal Chemistry (2017)
37. New Imidazo[1,2-A]Pyridin-2-Yl Derivatives As Ache, Bche, and Lox Inhibitors; Design, Synthesis, and Biological Evaluation, Letters in Drug Design and Discovery (2023)
38. 4-Oxobenzo[D]1,2,3-Triazin-Pyridinium-Phenylacetamide Derivatives As New Anti-Alzheimer Agents: Design, Synthesis, in Vitro Evaluation, Molecular Modeling, and Molecular Dynamic Study, Structural Chemistry (2020)
39. Amino-7,8-Dihydro-4H-Chromenone Derivatives As Potential Inhibitors of Acetylcholinesterase and Butyrylcholinesterase for Alzheimer’S Disease Management; in Vitro and in Silico Study, BMC Chemistry (2024)
40. 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)
41. Synthesis, Docking Study and Neuroprotective Effects of Some Novel Pyrano[3,2-C]Chromene Derivatives Bearing Morpholine/Phenylpiperazine Moiety, Bioorganic and Medicinal Chemistry (2017)
42. Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study, Medicinal Chemistry Research (2019)
43. Cinnamon, a Promising Prospect Towards Alzheimer's Disease, Pharmacological Research (2018)
44. Design, Synthesis, Biological Evaluation, and Docking Study of Novel Dual-Acting Thiazole-Pyridiniums Inhibiting Acetylcholinesterase and Β-Amyloid Aggregation for Alzheimer's Disease, Bioorganic Chemistry (2020)
45. Novel N-Benzylpyridinium Moiety Linked to Arylisoxazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Evaluation, and Docking Study, Bioorganic Chemistry (2019)
46. Molecular Perception of Interactions Between Bis(7)Tacrine and Cystamine-Tacrine Dimer With Cholinesterases As the Promising Proposed Agents for the Treatment of Alzheimers Disease, Journal of Biomolecular Structure and Dynamics (2016)
47. 1,2,3-Triazole-Isoxazole Based Acetylcholinesterase Inhibitors: Synthesis, Biological Evaluation and Docking Study, Letters in Drug Design and Discovery (2017)
48. Design, Synthesis and Characterization of Novel Urolithin Derivatives As Cholinesterase Inhibitor Agents, Letters in Drug Design and Discovery (2018)
49. Design and Synthesis of Novel Coumarin-Pyridinium Hybrids: In Vitro Cholinesterase Inhibitory Activity, Bioorganic Chemistry (2018)