Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
New Classes of Carbazoles As Potential Multi-Functional Anti-Alzheimer's Agents Publisher Pubmed



Choubdar N1 ; Golshani M2 ; Jalilibaleh L2 ; Nadri H3 ; Kucukkilinc TT4 ; Ayazgok B4 ; Moradi A3 ; Moghadam FH5 ; Abdolahi Z3 ; Ameri A6 ; Salehian F2 ; Foroumadi A2 ; Khoobi M2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Organic Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, Turkey
  5. 5. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
  6. 6. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

Source: Bioorganic Chemistry Published:2019


Abstract

Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11–36.5 µM and 0.02–98.6 µM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Aβ1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease. © 2019 Elsevier Inc.
Related Docs
View other Related Docs
1. Chromone–Lipoic Acid Conjugate: Neuroprotective Agent Having Acceptable Butyrylcholinesterase Inhibition, Antioxidant and Copper-Chelation Activities, DARU# Journal of Pharmaceutical Sciences (2021)
2. Novel 3-Phenylcoumarin–Lipoic Acid Conjugates As Multi-Functional Agents for Potential Treatment of Alzheimer's Disease, Bioorganic Chemistry (2018)
3. Chromone Derivatives Bearing Pyridinium Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Bioorganic Chemistry (2021)
4. Synthesis and Biological Evaluation of New N-Benzylpyridinium-Based Benzoheterocycles As Potential Anti-Alzheimer's Agents, Bioorganic Chemistry (2019)
5. 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)
6. A Review on Tacrine-Based Scaffolds As Multi-Target Drugs (Mtdls) for Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)
7. 3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety As Multi-Target-Directed Ligands Against Alzheimer's Disease, Chemistry and Biodiversity (2019)
8. Novel 3-Aminobenzofuran Derivatives As Multifunctional Agents for the Treatment of Alzheimer’S Disease, Frontiers in Chemistry (2022)
Experts (# of related papers)
View all Related Experts
Mohammad Mahdavi (22)
Alireza Foroumadi (21)
Other Related Docs
9. 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)
10. 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)
11. 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)
12. Design and Synthesis of Benzodiazepine-1,2,3-Triazole Hybrid Derivatives As Selective Butyrylcholinesterase Inhibitors, Molecular Diversity (2020)
13. 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)
14. Design and Synthesis of Multi-Target Directed 1,2,3-Triazole-Dimethylaminoacryloyl-Chromenone Derivatives With Potential Use in Alzheimer's Disease, BMC Chemistry (2020)
15. Novel Coumarin–Pyridine Hybrids As Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer’S Disease, Frontiers in Chemistry (2022)
16. 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)
17. Anticholinesterase Activity of Cinnamic Acids Derivatives: In Vitro, in Vivo Biological Evaluation, and Docking Study, Letters in Drug Design and Discovery (2020)
18. Novel Tacrine-Based Acetylcholinesterase Inhibitors As Potential Agents for the Treatment of Alzheimer’S Disease: Quinolotacrine Hybrids, Molecular Diversity (2022)
19. Design and Synthesis of Novel Anti-Alzheimer's Agents: Acridine-Chromenone and Quinoline-Chromenone Hybrids, Bioorganic Chemistry (2016)
20. Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study, Medicinal Chemistry Research (2019)
21. 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)
22. 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)
23. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents, Chemistry and Biodiversity (2019)
24. Coumarin Derivatives Bearing Benzoheterocycle Moiety: Synthesis, Cholinesterase Inhibitory, and Docking Simulation Study, Iranian Journal of Basic Medical Sciences (2017)
25. Design, Synthesis, and Biological Evaluation of Selective and Potent Carbazole-Based Butyrylcholinesterase Inhibitors, Bioorganic and Medicinal Chemistry (2018)
26. 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)
27. Synthesis and Cholinesterase Inhibitory Activity of New 2-Benzofuran Carboxamide-Benzylpyridinum Salts, Bioorganic Chemistry (2018)
28. 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)
29. Pelargonidin Improves Memory Deficit in Amyloid Β25-35 Rat Model of Alzheimer's Disease by Inhibition of Glial Activation, Cholinesterase, and Oxidative Stress, Biomedicine and Pharmacotherapy (2016)
30. 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)
31. Lipoic Acid Scaffold Applications in the Design of Multitarget-Directed Ligands Against Alzheimer's Disease, Bioorganic Chemistry (2025)
32. Design, Synthesis, Molecular Modeling and Anticholinesterase Activity of Benzylidene-Benzofuran-3-Ones Containing Cyclic Amine Side Chain, Future Medicinal Chemistry (2017)
33. 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)
34. Synthesis and Anticholinergic Activity of 4-Hydroxycoumarin Derivatives Containing Substituted Benzyl-1,2,3-Triazole Moiety, Chemical Biology and Drug Design (2015)
35. Investigation of Polysaccharide Extracts From Iranian and French Strains of Agaricus Subrufescens Against Enzymes Involved in Alzheimer’S Disease; [Investigacion De Extractos De Polisacaridos De Cepas Iranies Y Francesas De Agaricus Subrufescens Contra Enzimas Relevantes Para La Enfermedad De Alzheimer], Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas (2019)
36. Investigation of Alpha-Lipoic Acid Effect on Memory Impairment Considering Strain-Dependent Differences in Mice, Life Sciences (2021)
37. Synthesis, Docking Study and Neuroprotective Effects of Some Novel Pyrano[3,2-C]Chromene Derivatives Bearing Morpholine/Phenylpiperazine Moiety, Bioorganic and Medicinal Chemistry (2017)
38. 1,2,3-Triazole-Isoxazole Based Acetylcholinesterase Inhibitors: Synthesis, Biological Evaluation and Docking Study, Letters in Drug Design and Discovery (2017)
39. Design, Synthesis, and Molecular Docking of Some Novel Tacrine Based Cyclopentapyranopyridine- and Tetrahydropyranoquinoline-Kojic Acid Derivatives As Anti-Acetylcholinesterase Agents, Chemistry and Biodiversity (2021)
40. Synthesis, Docking Study, and Biological Evaluation of Novel Umbellipherone/Hymecromone Derivatives As Acetylcholinesterase/Butyrylcholinesterase Inhibitors, Medicinal Chemistry Research (2018)
41. Synthesis, and in Vitro Biological Evaluations of Novel Naphthoquinone Conjugated to Aryl Triazole Acetamide Derivatives As Potential Anti-Alzheimer Agents, Journal of Molecular Structure (2022)
42. Synthesis of Novel Chromenones Linked to 1,2,3-Triazole Ring System: Investigation of Biological Activities Against Alzheimer's Disease, Bioorganic Chemistry (2017)
43. Design and Synthesis of Novel Arylisoxazole-Chromenone Carboxamides: Investigation of Biological Activities Associated With Alzheimer's Disease, Chemistry and Biodiversity (2020)
44. Design, Synthesis, Characterization, Enzymatic Inhibition Evaluations, and Docking Study of Novel Quinazolinone Derivatives, International Journal of Biological Macromolecules (2021)
45. Can Marine Products Improve Alzheimer’S Disease, Journal of Sciences# Islamic Republic of Iran (2020)