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

Year 2026, Volume: 47 Issue: 1, 103 - 109, 27.02.2026

Özge Güngör

https://doi.org/10.17776/csj.1773859
https://izlik.org/JA25SS75HD

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
There are 25 citations in total.

Details

Primary Language English
Subjects Enzymes, Organic Chemical Synthesis
Journal Section Research Article
Authors

Özge Güngör 0000-0003-3529-2704

Submission Date August 29, 2025
Acceptance Date January 16, 2026
Publication Date February 27, 2026
DOI https://doi.org/10.17776/csj.1773859
IZ https://izlik.org/JA25SS75HD
Published in Issue Year 2026 Volume: 47 Issue: 1

Cite

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

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