Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox Publisher Pubmed



Pourabdi L1 ; Khoobi M2, 3 ; Nadri H4 ; Moradi A4 ; Moghadam FH5 ; Emami S6 ; Mojtahedi MM1 ; Haririan I2 ; Forootanfar H7 ; Ameri A8 ; Foroumadi A3 ; Shafiee A3
Authors

Source: European Journal of Medicinal Chemistry Published:2016


Abstract

A series of tacrine-based pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolines and related compounds were designed and synthesized for targeting AChE, BuChE and 15-LOX enzymes in the field of Alzheimer's disease therapy. Most of compounds showed potent activity against cholinesterases and mild potency toward 15-LOX enzyme. In particular, compounds 29, 32 and 40 displayed inhibition at nano-molar level against AChE and BuChE (IC50s = 0.005–0.08 μM), being more potent than reference drug tacrine. Moreover, compound 32 with IC50value of 31 μM was the most potent compound against 15-LOX. The cytotoxicity assay on HepG2 cells revealed that compounds 29 and 32 showed no significant cytotoxic activity even at concentration of 50 μM. The cytotoxicity of compounds 29 and 32 was significantly less than that of tacrine at higher concentrations. © 2016 Elsevier Masson SAS
Related Docs
View other Related Docs
1. 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)
2. Novel Tacrine-Based Pyrano[3’,4’:5,6]Pyrano[2,3-B]Quinolinones: Synthesis and Cholinesterase Inhibitory Activity, Archiv der Pharmazie (2016)
3. Synthesis and Anticancer Activity of 1,3,5-Triaryl-1H-Pyrazole, Letters in Drug Design and Discovery (2015)
Experts (# of related papers)
View all Related Experts
Mohammad Mahdavi (12)
Bagher Larijani (8)
Other Related Docs
4. 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)
5. Novel Diazen-Bis(Phenoxy-1,2,3-Triazole-N-Phenylacetamide) Derivatives As Potent Anti-Cholinesterase, Anti-Α-Glycosidase and Anti-Α-Amylase Agents: In Vitro and in Silico Evaluations, Journal of Molecular Structure (2025)
6. Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs As Potent Anti-Alzheimer's Agents, Chemistry and Biodiversity (2019)
7. Cinnamic Acid Conjugated With Triazole Acetamides As Anti-Alzheimer and Anti-Melanogenesis Candidates: An in Vitro and in Silico Study, Scientific Reports (2025)
8. Anticholinesterase Activities of Novel Isoindolin-1,3-Dione-Based Acetohydrazide Derivatives: Design, Synthesis, Biological Evaluation, Molecular Dynamic Study, BMC Chemistry (2024)
9. 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)
10. Synthesis, Biological Evaluation and Molecular Modeling Studies of Methyl Indole-Isoxazole Carbohydrazide Derivatives As Multi-Target Anti-Alzheimer’S Agents, Scientific Reports (2024)
11. Novel N-Benzylpiperidine Derivatives of 5-Arylisoxazole-3-Carboxamides As Anti-Alzheimer's Agents, Archiv der Pharmazie (2021)
12. 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)
13. N-Cyclohexylimidazo[1,2-A]Pyridine Derivatives As Multi-Target-Directed Ligands for Treatment of Alzheimer's Disease, Bioorganic Chemistry (2020)
14. Phenyl-Quinoline Derivatives As Lead Structure of Cholinesterase Inhibitors With Potency to Reduce the Gsk-3Β Level Targeting Alzheimer's Disease, International Journal of Biological Macromolecules (2023)
15. A Review on Tacrine-Based Scaffolds As Multi-Target Drugs (Mtdls) for Alzheimer's Disease, European Journal of Medicinal Chemistry (2017)
16. Synthesis, Molecular Docking Study, and Cytotoxic Activity of 1,3,5-Triaryl Pyrazole Derivatives, Letters in Drug Design and Discovery (2016)
17. 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)
18. New 1E,1′E-Hydrazine-Bis(Phenoxy-1,2,3-Triazol-Acetamide) Derivatives As Potent Inhibitors Against Acetylcholinesterase, Butyrylcholinesterase, and Α-Glucosidase, RSC Advances (2025)
19. 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)
20. Rhodanine-Pyridinium Derivatives As a New Category of Cholinesterase Inhibitors: Design, Synthesis, in Vitro and in Silico Enzymatic Evaluations, International Journal of Biological Macromolecules (2025)