Acetylcholinesterase Inhibition Properties and Docking Studies of Compounds Based on 6-Hydrazinyl-1,3,4-Trimethyl-1H-Pyrazolo[3,4-b]Pyridine

Year 2023, , 21 - 30, 28.02.2023

Seyit Ali Güngör

https://doi.org/10.18596/jotcsa.1117324

Abstract

New compounds based on 6-hydrazinyl-1,3,4-trimethyl-1H-pyrazolo[3,4-b]pyridine (3a and 3b) were synthesized and characterized by FTIR and 1H/13C NMR spectroscopic methods and their in vitro acetylcholinesterase (AChE) inhibition studies were evaluated. Compound 3b (IC50 value 104.4 µM) exhibited stronger AChE inhibitory activity than the reference galantamine compound (IC50 value 139.4 µM). Molecular docking studies were performed to determine the key interactions and possible binding modes between AChE of compounds. The most active one, 3b, showed a binding affinity of -10.28 kcal/mol.

Keywords

Synthesis, AChE inhibition, Docking

References

• 1. Khachaturian ZS. Conference R Diagnosis of Alzheimer’s Disease. Arizona Heal Sci Libr User. 1985;42:1097–105.
• 2. Sharma K. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review). Mol Med Rep. 2019;20(2):1479–87.
• 3. Cheng ST. Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities. Curr Psychiatry Rep. 2016;18(9).
• 4. Maxwell CJ, Vu M, Hogan DB, Patten SB, Jantzi M, Kergoat MJ, et al. Patterns and determinants of dementia pharmacotherapy in a population-based cohort of home care clients. Drugs and Aging. 2013;30(7):569–85.
• 5. Silman I, Sussman JL. Acetylcholinesterase: “Classical” and “non-classical” functions and pharmacology. Curr Opin Pharmacol. 2005;5(3 SPEC. ISS.):293–302.
• 6. Birks JS. Cholinesterase inhibitors (ChEIs), donepezil, galantamine and rivastigmine are efficacious for mild to moderate Alzheimer’s disease. 2012;(5).
• 7. Tschanz JT, Corcoran CD, Schwartz S, Treiber K, Green RC, Norton MC, et al. Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with alzheimer dementia: The cache county dementia progression study. Am J Geriatr Psychiatry. 2011;19(6):532–42.
• 8. Parsons C, Lim WY, Loy C, McGuinness B, Passmore P, Ward SA, et al. Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia. Cochrane Database Syst Rev. 2021;2021(1).
• 9. Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology. 2001;57(4):613–20.
• 10. Selvarani V, Annaraj B, Neelakantan MA, Sundaramoorthy S, Velmurugan D. Synthesis and crystal structure of hydroxyacetophenone Schiff bases containing propargyl moiety: Solvent effects on UV-visible spectra. Spectrochim Acta - Part A Mol Biomol Spectrosc. 2012;91:329–37.
• 11. Güngör SA, Tümer M, Köse M, Erkan S. Benzaldehyde derivatives with functional propargyl groups as α-glucosidase inhibitors. J Mol Struct. 2020;1206.
• 12. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7(2):88–95.
• 13. Güngör Ö, Köse M. Design, synthesis and biological evaluation of biguanids and biguanid-sulfonamides as cholinesterase inhibitors. J Mol Struct. 2022;1260.
• 14. Allouche A. Software News and Updates Gabedit — A Graphical User Interface for Computational Chemistry Softwares. J Comput Chem. 2012;32:174–82.
• 15. Şahin İ, Bingöl Z, Onur S, Güngör SA, Köse M, Gülçin İ, et al. Enzyme Inhibition Properties and Molecular Docking Studies of 4‐Sulfonate Containing Aryl α‐Hydroxyphosphonates Based Hybrid Molecules. Chem Biodivers. 2022;
• 16. BIOVIA DS. Discovery studio visualizer. In San Diego, CA, USA; 2017. p. 298.
• 17. Lill MA, Danielson ML. Computer-aided drug design platform using PyMOL. J Comput Aided Mol Des. 2011;25(1):13–9.