Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety

Özge Güngör

doi:10.17776/csj.1773859

Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety

Abstract

The focus of this study was the preparation and structural characterisation of hydrazine hydrazone Schiff base compounds containing a propargyl group in a new structure, using common spectroscopic and analytical methods. Since Hydrazide-hydrazone compounds are known to possess high biological activity, it was thought that compound 2a synthesized by us could be an important inhibitor for the treatment of Alzheimer's disease. A screening was performed on the Hydrazide-hydrazone Schiff base compound (2a) to determine its potential as an inhibitor of cholinesterase. The enzyme inhibition values of compound 2a were determined as IC₅₀= 42.72±0.01 and IC₅₀= 39.19±0.04 µM for AChE and BuChE, respectively. Compared to the standard compound Galantamine (IC₅₀= 32.45±0.06 and IC₅₀= 40.25±0.03 µM), it exhibited low activity for AChE. It exhibited a higher activity for BuChE. When compared to the standard drug galantamine, the compound showed only moderate inhibitory activity. Ki values of 1.25 and 2.32 μM were determined as the substance exhibited milder activity against AChE and BuChE, respectively. Molecular docking studies also revealed that these hydrophilic and hydrophobic interactions are instrumental in conferring the compound's strong binding affinity. They also revealed that these interactions are instrumental in the compound's potent inhibitory activity. These results indicate that compound 2a exhibits activity against both enzymes.

Keywords

Enzyme inhibition, Hydrazide-hydrazone, Molecular docking studies

References

[1] Walczak-Nowicka, Ł. J., & Herbet, M. (2021). Acetylcholinesterase inhibitors in the treatment of neurodegenerative diseases and the role of acetylcholinesterase in their pathogenesis. International Journal of Molecular Sciences, 22(17), 9290. https://doi.org/10.3390/ijms22179290
[2] Milelli, A. (2009). New synthetic polyamines as multi-target-directed ligands for the treatment of Alzheimer’s disease and cancer: Design, synthesis and biological evaluation [Doktora tezi, Bologna Üniversitesi].
[3] Brenner, T., Nizri, E., Irony-Tur-Sinai, M., Hamra-Amitay, Y., & Wirguin, I. (2008). Acetylcholinesterase inhibitors and cholinergic modulation in myasthenia gravis and neuroinflammation. Journal of Neuroimmunology, 201–202, 121–127. https://doi.org/10.1016/j.jneuroim.2008.05.022
[4] Mehta, M., Adem, A., & Sabbagh, M. (2012). New acetylcholinesterase inhibitors for Alzheimer’s disease. International Journal of Alzheimer's Disease, 2012, 728983. https://doi.org/10.1155/2012/728983
[5] Fujimoto, K. I. (2011). [Memantine]. Nihon Rinsho, 69(1), 41–46.
[6] De, S., Kumar, S. K., Shah, S. K., Kazi, S., Sarkar, N., Banerjee, S., & Dey, S. (2022). Pyridine: The scaffolds with significant clinical diversity. RSC Advances, 12(24), 15385–15406. https://doi.org/10.1039/D2RA01571D
[7] Güngör, S. A. (2023). Synthesis, in silico and in vitro studies of hydrazide-hydrazone imine derivatives as potential cholinesterase inhibitors. Chemical Biology & Drug Design, 102(3), 676–691. https://doi.org/10.1039/D4MD00495G
[8] Markova, N. V., Rogojerov, M. I., Angelova, V. T., & Vassilev, N. G. (2019). Experimental and theoretical conformational studies of hydrazine derivatives bearing a chromene scaffold. Journal of Molecular Structure, 1198, 126880. https://doi.org/10.1016/j.molstruc.2019.126880
[9] Elçin, O., Seda, U., Fatma, K., & Nathaly, S. (2006). Synthesis and characterization of novel hydrazide-hydrazones and the study of their structure-antituberculosis activity. Letters in Drug Design & Discovery, 3(41), 1253–1261. https://doi.org/10.1016/j.ejmech.2006.06.009
[10] Houghton, P. J. (2009). Acetylcholinesterase inhibitors of natural origin. CRC Press.

[11] Abdel-Motaal, M., & Nabil, A. (2018). Biological activity of some newly synthesized hydrazone derivatives derived from (dicyclopropylmethylene) hydrazone. European Chemical Bulletin, 7(9), 280–287. https://doi.org/10.17628/ECB.2018.7.280-287
[12] Moussa, Z., Al-Mamary, M., Al-Juhani, S., & Ahmed, S. A. (2020). Preparation and biological assessment of some aromatic hydrazones derived from hydrazides of phenolic acids and aromatic aldehydes. Heliyon, 6(10), e05019. https://doi.org/10.1016/j.heliyon.2020.e05019
[13] Le Goff, G., & Ouazzani, J. (2014). Natural hydrazine-containing compounds: Biosynthesis, isolation, biological activities and synthesis. Bioorganic & Medicinal Chemistry, 22(23), 6529–6544. https://doi.org/10.1016/j.bmc.2014.10.011
[14] Verma, G., Marella, A., Shaquiquzzaman, M., Akhtar, M., Ali, M. R., & Alam, M. M. (2014). A review article on hydrazones. International Journal of Pharmaceutical Sciences and Research, 6(1), 69–80. https://doi.org/10.4103/0975-7406.129170
[15] Rollas, S., & Küçükgüzel, Ş. G. (2007). Biological activities of hydrazone derivatives. Molecules, 12(8), 1910–1939. https://doi.org/10.3390/12081910
[16] Ali, A. A., Ismail, M. A., Elgammal, W. E., Belal, A., Obaidullah, A. J., Khalil, A. K., Elhagali, G. A. M., & El-Gaby, M. S. A. (2025). Novel azo dyes containing a hydrazide-hydrazone moiety for dyeing polyester fabric. Scientific Reports, 15, 1–20. https://doi.org/10.1038/s41598-024-83565-3
[17] Songül, Ş. (2023). A new hydrazide-hydrazone based Schiff base: Synthesis, DFT calculations, in silico pharmacokinetics and toxicity, inhibitory activity against tau aggregation and SARS-CoV-2 Mpro. Journal of Molecular Structure, 1271, 134042. https://doi.org/10.30492/ijcce.2022.559865.5508
[18] Gözcelioğlu, B., Uras, İ. S., Şentürk, M., & Konuklugil, B. (2023). Exploring the enzyme inhibitory properties of Antarctic algal extracts. Turkish Journal of Biochemistry, 48(5), 592–602. https://doi.org/10.1515/tjb-2023-0103
[19] Güngör, S. A., Tümer, M., Köse, M., & Erkan, S. (2022). N-substituted benzenesulfonamide compounds: DNA binding properties and molecular docking studies. Journal of Biomolecular Structure and Dynamics, 40(16), 7424–7438. https://doi.org/10.1080/07391102.2021.1897683
[20] Erdogan, E., Güngör, O., Güngör, S. A., & Köse, M. (2025). New 1,2,3-triazole-quinazolinone skeleton as potential cholinesterase and α-amylase inhibitors: In vitro and in silico studies. Journal of Molecular Liquids, 424, 124350. https://doi.org/10.1016/j.molliq.2025.126986
[21] Chen, L., Du, J., Dai, Q., Zhang, H., Pang, W., & Hu, J. (2014). Prediction of anti-tumor chemical probes of a traditional Chinese medicine formula by HPLC fingerprinting combined with molecular docking. European Journal of Medicinal Chemistry, 83, 294–306. https://doi.org/10.1016/j.ejmech.2014.06.037
[22] Aispuro-Pérez, A., López-Ávalos, J., García-Páez, F., Montes-Avila, J., Picos-Corrales, L. A., Ochoa-Terán, A., Bastidas, P., Montaño, S., Calderón-Zamora, L., Osuna-Martínez, U., & Sarmiento-Sánchez, J. I. (2020). Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors. Bioorganic Chemistry, 94, 103434. https://doi.org/10.1016/j.bioorg.2019.103491
[23] Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19(14), 1639–1662. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1575::AID-JCC3>3.0.CO;2-G
[24] Dassault Systèmes. (2021). BIOVIA Discovery Studio visualizer (Release 2021). Dassault Systèmes.
[25] Lill, M. A., & Danielson, M. L. (2011). Computer-aided drug design platform using PyMOL. Journal of Computer-Aided Molecular Design, 25(1), 13–19. https://doi.org/10.1007/s10822-010-9395-8

Details

Primary Language

English

Subjects

Enzymes, Organic Chemical Synthesis

Journal Section

Research Article

Authors

Özge Güngör ^*
0000-0003-3529-2704
Türkiye

Publication Date

February 27, 2026

Submission Date

August 29, 2025

Acceptance Date

January 16, 2026

Published in Issue

Year 2026 Volume: 47 Number: 1

DOI

https://doi.org/10.17776/csj.1773859

IZ

https://izlik.org/JA25SS75HD

APA

Güngör, Ö. (2026). Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety. Cumhuriyet Science Journal, 47(1), 103-109. https://doi.org/10.17776/csj.1773859

AMA

1.Güngör Ö. Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety. CSJ. 2026;47(1):103-109. doi:10.17776/csj.1773859

Chicago

Güngör, Özge. 2026. “Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl Pyridine Moiety”. Cumhuriyet Science Journal 47 (1): 103-9. https://doi.org/10.17776/csj.1773859.

EndNote

Güngör Ö (February 1, 2026) Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety. Cumhuriyet Science Journal 47 1 103–109.

IEEE

[1]Ö. Güngör, “Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety”, CSJ, vol. 47, no. 1, pp. 103–109, Feb. 2026, doi: 10.17776/csj.1773859.

ISNAD

Güngör, Özge. “Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl Pyridine Moiety”. Cumhuriyet Science Journal 47/1 (February 1, 2026): 103-109. https://doi.org/10.17776/csj.1773859.

JAMA

1.Güngör Ö. Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety. CSJ. 2026;47:103–109.

MLA

Güngör, Özge. “Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl Pyridine Moiety”. Cumhuriyet Science Journal, vol. 47, no. 1, Feb. 2026, pp. 103-9, doi:10.17776/csj.1773859.

Vancouver

1.Özge Güngör. Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety. CSJ. 2026 Feb. 1;47(1):103-9. doi:10.17776/csj.1773859

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December

Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety

Abstract

Keywords

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite