Research Article

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

Number: 2026 September 3, 2026
TR EN

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

Abstract

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.

Keywords

Acetylcholinesterase, Alzheimer, Butyrylcholinesterase, Phthalonitrile

Supporting Institution

Giresun University

Project Number

FEN-BAP-A-090323-34

Ethical Statement

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

Thanks

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.

References

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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. JAES. 2026;(2026). doi:10.35229/jaes.1929402
Chicago
Tekin, Aşkın, Esra Özbek Mercan, and Tayfun Arslan. 2026. “Synthesis, Molecular Modeling, and AChE BChE Inhibitory Activity of Novel Phthalonitriles”. Journal of Anatolian Environmental and Animal Sciences, nos. 2026. https://doi.org/10.35229/jaes.1929402.
EndNote
Tekin A, Özbek Mercan E, Arslan T (September 1, 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, and T. Arslan, “Synthesis, molecular modeling, and AChE/BChE inhibitory activity of novel phthalonitriles”, JAES, no. 2026, Sept. 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 (September 1, 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. JAES. 2026. doi:10.35229/jaes.1929402.
MLA
Tekin, Aşkın, et al. “Synthesis, Molecular Modeling, and AChE BChE Inhibitory Activity of Novel Phthalonitriles”. Journal of Anatolian Environmental and Animal Sciences, no. 2026, Sept. 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. JAES. 2026 Sep. 1;(2026). doi:10.35229/jaes.1929402