Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):

Share this content! On (X network) By

Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study Publisher

Faraji L¹ ; Nadri H² ; Moradi A² ; Bukhari SNA³ ; Pakseresht B⁴ ; Moghadam FH⁵ ; Moghimi S¹ ; Abdollahi M^{1, 6} ; Khoobi M^{1, 7} ; Foroumadi A^{8, 9}

Show Affiliations

1. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
2. Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3. Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka, 2014, Saudi Arabia
4. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
5. Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran, Iran
6. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
8. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
9. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Medicinal Chemistry Research Published:2019

Abstract

In this manuscript, 17 aminoalkyl-substituted flavonoid derivatives were synthesized and their anticholinesterase, anti-beta-amyloid (Aβ) aggregation and neuroprotective activities were evaluated. The synthesized compounds were prepared through four-step reaction, started from the reaction between 2-hydroxyacetophenone and 4-methoxy benzaldehyde. Among the final compounds, 6j displayed the best anti-butyrylcholinesterase activity (IC50 = 0.335 μM). Moreover, compound 6i significantly protected PC12 neurons against H2O2-induced cell death. This compound could also inhibit acetylcholinesterase and self-induced Aβ peptide aggregation by 51.3% and 49.2%, respectively. The results indicated that compound 6i could be considered as a lead compound towards the discovery of disease-modifying drugs for Alzheimer’s disease (AD) therapy. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Related Docs

View other Related Docs

1. 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)

2. A Review on Flavonoid-Based Scaffolds As Multi-Target-Directed Ligands (Mtdls) for Alzheimer's Disease, European Journal of Medicinal Chemistry (2018)

3. 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)

4. Coumarin Derivatives Bearing Benzoheterocycle Moiety: Synthesis, Cholinesterase Inhibitory, and Docking Simulation Study, Iranian Journal of Basic Medical Sciences (2017)

5. Cholinesterase Inhibition Activity and Docking Simulation Study of Coumarin Mannich Base Derivatives, Journal of Sciences# Islamic Republic of Iran (2019)

6. Anticholinesterase Activity of Cinnamic Acids Derivatives: In Vitro, in Vivo Biological Evaluation, and Docking Study, Letters in Drug Design and Discovery (2020)

7. Chromone Derivatives Bearing Pyridinium Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Bioorganic Chemistry (2021)

8. 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)

Experts (# of related papers)

View all Related Experts

Alireza Foroumadi (31)

Mohammad Mahdavi (28)

Other Related Docs

9. 3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Chemistry and Biodiversity (2019)

10. Novel 3-Aminobenzofuran Derivatives As Multifunctional Agents for the Treatment of Alzheimer’S Disease, Frontiers in Chemistry (2022)

11. 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)

12. 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)

13. Chromone–Lipoic Acid Conjugate: Neuroprotective Agent Having Acceptable Butyrylcholinesterase Inhibition, Antioxidant and Copper-Chelation Activities, DARU# Journal of Pharmaceutical Sciences (2021)

14. A Review on Tacrine-Based Scaffolds As Multi-Target Drugs (Mtdls) for Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)

15. Novel 3-Phenylcoumarin–Lipoic Acid Conjugates As Multi-Functional Agents for Potential Treatment of Alzheimer's Disease, Bioorganic Chemistry (2018)

16. Synthesis and Cholinesterase Inhibitory Activity of New 2-Benzofuran Carboxamide-Benzylpyridinum Salts, Bioorganic Chemistry (2018)

17. Synthesis, Docking Study, and Biological Evaluation of Novel Umbellipherone/Hymecromone Derivatives As Acetylcholinesterase/Butyrylcholinesterase Inhibitors, Medicinal Chemistry Research (2018)

18. Design, Synthesis, Molecular Modeling and Anticholinesterase Activity of Benzylidene-Benzofuran-3-Ones Containing Cyclic Amine Side Chain, Future Medicinal Chemistry (2017)

19. New Classes of Carbazoles As Potential Multi-Functional Anti-Alzheimer's Agents, Bioorganic Chemistry (2019)

20. Novel Tacrine-1,2,3-Triazole Hybrids: In Vitro, in Vivo Biological Evaluation and Docking Study of Cholinesterase Inhibitors, European Journal of Medicinal Chemistry (2017)

21. Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone-1,2,4-Oxadiazole-1,2,3-Triazole Hybrids, Chemical Biology and Drug Design (2015)

22. Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors, Bioorganic and Medicinal Chemistry (2018)

23. Potent Acetylcholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, and Docking Study of Acridone Linked to 1,2,3-Triazole Derivatives, European Journal of Medicinal Chemistry (2015)

24. Hetero-Annulated Coumarins As New Ache/Buche Inhibitors: Synthesis and Biological Evaluation, Medicinal Chemistry Research (2016)

25. Design, Synthesis, and Cholinesterase Inhibition Assay of Coumarin-3-Carboxamide-N-Morpholine Hybrids As New Anti-Alzheimer Agents, Chemistry and Biodiversity (2019)

26. Design of Peptide-Based Inhibitor Agent Against Amyloid-Β Aggregation: Molecular Docking, Synthesis and in Vitro Evaluation, Bioorganic Chemistry (2020)

27. Design, Synthesis and Anti-Alzheimer's Activity of Novel 1,2,3-Triazole-Chromenone Carboxamide Derivatives, Bioorganic Chemistry (2019)

28. Design, Synthesis, and Evaluation of Novel Cinnamic Acid-Tryptamine Hybrid for Inhibition of Acetylcholinesterase and Butyrylcholinesterase, DARU# Journal of Pharmaceutical Sciences (2020)

29. 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)

30. Synthesis and Biological Evaluation of 5-Benzylidenerhodanine-3-Acetic Acid Derivatives As Ache and 15-Lox Inhibitors, Journal of Enzyme Inhibition and Medicinal Chemistry (2015)

31. Design, Synthesis and Characterization of Novel Urolithin Derivatives As Cholinesterase Inhibitor Agents, Letters in Drug Design and Discovery (2018)

32. New Tacrine-Derived Ache/Buche Inhibitors: Synthesis and Biological Evaluation of 5-Amino-2-Phenyl-4H-Pyrano[2,3-B]Quinoline-3-Carboxylates, European Journal of Medicinal Chemistry (2017)

33. Satureja Bachtiarica Ameliorate Beta-Amyloid Induced Memory Impairment, Oxidative Stress and Cholinergic Deficit in Animal Model of Alzheimer’S Disease, Metabolic Brain Disease (2016)

34. Synthesis and Antiacetylcholinesterase Activity Evaluation of New 2-Aryl Benzofuran Derivatives, Letters in Drug Design and Discovery (2016)

35. An Efficient Approach to the Synthesis of Coumarin-Fused Dihydropyridinones, Heterocyclic Communications (2017)

36. Multifunctional Iminochromene-2H-Carboxamide Derivatives Containing Different Aminomethylene Triazole With Bace1 Inhibitory, Neuroprotective and Metal Chelating Properties Targeting Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)

37. Synthesis and Anticholinergic Activity of 4-Hydroxycoumarin Derivatives Containing Substituted Benzyl-1,2,3-Triazole Moiety, Chemical Biology and Drug Design (2015)

38. Synthesis, Docking Study and Neuroprotective Effects of Some Novel Pyrano[3,2-C]Chromene Derivatives Bearing Morpholine/Phenylpiperazine Moiety, Bioorganic and Medicinal Chemistry (2017)

39. Synthesis, Docking, Pharmacokinetic Prediction, and Acetylcholinesterase Inhibitory Evaluation of N-(2-(Piperidine-1-Yl)Ethyl)Benzamide Derivatives As Potential Anti-Alzheimer Agents, Research in Pharmaceutical Sciences (2024)

40. In Vitro Cholinesterase Inhibitory Activity of Some Plants Used in Iranian Traditional Medicine, Natural Product Research (2017)

41. 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)

42. Synthesis and Evaluation of Coumarin-Resveratrol Hybrids As 15-Lipoxygenaze Inhibitors, Synthetic Communications (2015)

43. Design, Synthesis and Biological Assessment of New 1-Benzyl-4-((4-Oxoquinazolin-3(4H)-Yl)Methyl) Pyridin-1-Ium Derivatives (Bops) As Potential Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase, Heliyon (2021)

44. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents, Chemistry and Biodiversity (2019)

45. 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)

46. Synthesis and Biological Evaluation of New N-Benzylpyridinium-Based Benzoheterocycles As Potential Anti-Alzheimer's Agents, Bioorganic Chemistry (2019)

47. Chemical Composition, Cholinesterase, and Α-Glucosidase Inhibitory Activity of the Essential Oils of Some Iranian Native Salvia Species, BMC Complementary Medicine and Therapies (2023)

48. Role of Natural Products for the Treatment of Alzheimer's Disease, European Journal of Pharmacology (2021)

49. Novel Tacrine-Based Acetylcholinesterase Inhibitors As Potential Agents for the Treatment of Alzheimer’S Disease: Quinolotacrine Hybrids, Molecular Diversity (2022)

50. 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)

Style	Citing Format
MLA	Faraji L, et al.. "Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study." Medicinal Chemistry Research, vol. 28, no. 7, 2019, pp. 974-983.
APA	Faraji L, Nadri H, Moradi A, Bukhari SNA, Pakseresht B, Moghadam FH, Moghimi S, Abdollahi M, Khoobi M, Foroumadi A (2019). Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study. Medicinal Chemistry Research, 28(7), 974-983.
Chicago	Faraji L, Nadri H, Moradi A, Bukhari SNA, Pakseresht B, Moghadam FH, Moghimi S, Abdollahi M, Khoobi M, Foroumadi A. "Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study." Medicinal Chemistry Research 28, no. 7 (2019): 974-983.
Harvard	Faraji L et al. (2019) 'Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study', Medicinal Chemistry Research, 28(7), pp. 974-983.
Vancouver	Faraji L, Nadri H, Moradi A, Bukhari SNA, Pakseresht B, Moghadam FH, et al.. Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study. Medicinal Chemistry Research. 2019;28(7):974-983.
BibTex	@article{ author = {Faraji L and Nadri H and Moradi A and Bukhari SNA and Pakseresht B and Moghadam FH and Moghimi S and Abdollahi M and Khoobi M and Foroumadi A}, title = {Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study}, journal = {Medicinal Chemistry Research}, volume = {28}, number = {7}, pages = {974-983}, year = {2019} }
RIS	TY - JOUR AU - Faraji L AU - Nadri H AU - Moradi A AU - Bukhari SNA AU - Pakseresht B AU - Moghadam FH AU - Moghimi S AU - Abdollahi M AU - Khoobi M AU - Foroumadi A TI - Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study JO - Medicinal Chemistry Research VL - 28 IS - 7 SP - 974 EP - 983 PY - 2019 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract