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Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles

Sayı: 2026 3 Eylül 2026
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Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles

Öz

This study investigated the synthesis, structural characterisation, and inhibitory effects on acetylcholinesterase and butyrylcholinesterase enzymes of novel phthalonitrile derivatives that could be considered potential therapeutic agents for the treatment of Alzheimer's disease. Alzheimer's disease is a neurodegenerative disorder characterised by progressive memory loss and cognitive dysfunction, and supporting the cholinergic system plays a significant role in current symptomatic treatment approaches. In this context, phthalonitrile derivatives with potential biological activity were synthesised via Claisen-Schmidt condensation and Debus-Radziszewski reactions. The structures of the compounds obtained were confirmed using various spectroscopic methods, and their inhibitory activities on AChE and BChE enzymes were then evaluated under in vitro conditions. The findings revealed that all synthesised compounds exhibited significant inhibitory effects at low nanomolar levels against both enzymes. Specifically, compound B4, which contains an imidazole ring, showed the highest inhibitory activity on both acetylcholinesterase and butyrylcholinesterase, with a stronger effect than the reference compound tacrine. Furthermore, molecular docking studies supported the finding that compound B4 demonstrated high binding affinity to the active sites of both enzymes and formed strong enzyme-ligand interactions. These results suggest that phthalonitrile derivatives, particularly compound B4, are promising candidates for the development of novel cholinesterase inhibitors for Alzheimer's disease.

Anahtar Kelimeler

Acetylcholinesterase, Alzheimer, Butyrylcholinesterase, Phthalonitrile

Destekleyen Kurum

Giresun University

Proje Numarası

FEN-BAP-A-090323-34

Etik Beyan

The author(s) declare that this study does not require ethical committee approval or any legal permission.

Teşekkür

This study was supported by the Research Fund of Giresun University (Project no: FEN-BAP-A-090323-34. We would like to thank the University of Giresun for financial support of this work.

Kaynakça

  1. Acar, İ., Arslan, T., Topçu, S., Aktaş, A., Şen, S., & Serencam, H. (2014). Synthesis and electrochemistry of metallophthalocyanines bearing {4-[(2E)-3-(3,4,5- trimethoxyphenyl) prop-2-enoyl] phenoxy} groups. Journal of Organometallic Chemistry, 752, 25-29. https://doi.org/10.1016/j.jorganchem.2013.11.021
  2. Armarego, W. L. F., & Perrin, D. D. (2002). Purification of laboratory chemicals (4th ed., reprint). Butterworth- Heinemann.
  3. Arslan, T. (2018a). An Efficient Synthesis of Novel Type Chalcones Containing 8-hydroxyquinoline Under Green Conditions. Erzincan University Journal of Science and Technology, 11(2), 321-327. https://doi.org/10.18185/erzifbed.422796
  4. Arslan, T. (2018b). Synthesis and Characterisation of New Sulfonamide Chalcones Containing an azo Group. Journal of Chemical Research, 42(5), 267-270. https://doi.org/10.3184/174751918X15269091219930
  5. Arslan, T. (2021). Design, synthesis of novel peripherally tetra- chalcone substituted phthalocyanines and their inhibitory effects on acetylcholinesterase and carbonic anhydrases (hCA I and II). Journal of Organometallic Chemistry, 951, 122021. https://doi.org/10.1016/j.jorganchem.2021.122021
  6. Arslan, T., & Tekin, A. (2022). Investigation of Cholinesterase Inhibitor Effects of Some Chalcone Substituted Metallophthalocyanines. Karadeniz Fen BilimLeri Dergisi, 12(2), 703-711. https://doi.org/10.31466/kfbd.1109715
  7. Arslan, T., Buğrahan Ceylan, M., Baş, H., Biyiklioglu, Z., & Senturk, M. (2020). Design, synthesis, characterization of peripherally tetra-pyridine-triazole-substituted phthalocyanines and their inhibitory effects on cholinesterases (AChE/BChE) and carbonic anhydrases (hCA I, II and IX). Dalton Transactions, 49(1), 203- 209. https://doi.org/10.1039/C9DT03897C
  8. Burmaoglu, S., Yilmaz, A. O., Taslimi, P., Algul, O., Kilic, D., & Gulcin, I. (2018). Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity. Archiv Der Pharmazie, 351(2). https://doi.org/10.1002/ardp.201700314
  9. Cavdar, H., Senturk, M., Guney, M., Durdagi, S., Kayik, G., Supuran, C. T., & Ekinci, D. (2019). Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: Kinetic and computational studies. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 429-437. https://doi.org/10.1080/14756366.2018.1543288
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Kaynak Göster

APA
Tekin, A., Özbek Mercan, E., & Arslan, T. (2026). Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles. Journal of Anatolian Environmental and Animal Sciences, 2026. https://doi.org/10.35229/jaes.1929402
AMA
1.Tekin A, Özbek Mercan E, Arslan T. Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles. Journal of Anatolian Environmental and Animal Sciences. 2026;(2026). doi:10.35229/jaes.1929402
Chicago
Tekin, Aşkın, Esra Özbek Mercan, ve Tayfun Arslan. 2026. “Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles”. Journal of Anatolian Environmental and Animal Sciences, sy 2026. https://doi.org/10.35229/jaes.1929402.
EndNote
Tekin A, Özbek Mercan E, Arslan T (01 Eylül 2026) Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles. Journal of Anatolian Environmental and Animal Sciences 2026
IEEE
[1]A. Tekin, E. Özbek Mercan, ve T. Arslan, “Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles”, Journal of Anatolian Environmental and Animal Sciences, sy 2026, Eyl. 2026, doi: 10.35229/jaes.1929402.
ISNAD
Tekin, Aşkın - Özbek Mercan, Esra - Arslan, Tayfun. “Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles”. Journal of Anatolian Environmental and Animal Sciences. 2026 (01 Eylül 2026). https://doi.org/10.35229/jaes.1929402.
JAMA
1.Tekin A, Özbek Mercan E, Arslan T. Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles. Journal of Anatolian Environmental and Animal Sciences. 2026. doi:10.35229/jaes.1929402.
MLA
Tekin, Aşkın, vd. “Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles”. Journal of Anatolian Environmental and Animal Sciences, sy 2026, Eylül 2026, doi:10.35229/jaes.1929402.
Vancouver
1.Aşkın Tekin, Esra Özbek Mercan, Tayfun Arslan. Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles. Journal of Anatolian Environmental and Animal Sciences. 01 Eylül 2026;(2026). doi:10.35229/jaes.1929402