Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors

Behiye Ateş; Fatih Dönmez; Meltem Tan Uygun

doi:10.12991/jrespharm.1897524

Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors

Abstract

In this study, a series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives (8a-i) were synthesized. The moleculer structures of the synthesized compounds were determined by 1H NMR, 13C NMR, and LC-MS/MS analyses. The inhibitory activities of the compounds against AChE and BuChE were evaluated. Compound 8e exhibited the highest inhibitory activity against AChE, with an IC50 value of 3.795 ± 0.057 µM, whereas compound 8h showed the highest inhibitory activity against BuChE, with an IC50 value of 15.484 ± 0.188 µM. The docking scores for compound 8e and donepezil were -8.39 and -11.06 kcal/mol, respectively. The selective acetylcholinesterase inhibitor 8e exhibited interaction patterns comparable to those of donepezil within the active site of AChE.

Keywords

Supporting Institution

The Scientific Research Projects Coordination Unit of Van Yüzüncü Yıl University

Project Number

TYL-2024-11283

Ethical Statement

Ethical approval is not required.

Thanks

This study was derived from the Master’s thesis of Behiye Ateş and was partially supported by the Scientific Research Projects Coordination Unit of Van Yüzüncü Yıl University (Project No: TYL-2024-11283).

References

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Details

Primary Language

English

Subjects

Pharmaceutical Biochemistry, Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Behiye Ateş
0009-0002-1243-2436
Türkiye

Fatih Dönmez
0000-0003-3958-1028
Türkiye

Meltem Tan Uygun ^*
0000-0003-4190-6047
Türkiye

Publication Date

October 6, 2026

Submission Date

February 25, 2026

Acceptance Date

August 1, 2026

Published in Issue

Year 2026 Volume: 30 Number: 5

DOI

https://doi.org/10.12991/jrespharm.1897524

IZ

https://izlik.org/JA62KF26WD

Cite

RIS / Bibtex

APA

Ateş, B., Dönmez, F., & Tan Uygun, M. (2026). Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors. Journal of Research in Pharmacy, 30(5), 1352-1367. https://doi.org/10.12991/jrespharm.1897524

AMA

1.Ateş B, Dönmez F, Tan Uygun M. Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors. J. Res. Pharm. 2026;30(5):1352-1367. doi:10.12991/jrespharm.1897524

Chicago

Ateş, Behiye, Fatih Dönmez, and Meltem Tan Uygun. 2026. “Synthesis, Cholinesterase Inhibitory Activity, and in Silico Studies of Novel Pyrazolopyrazine Derivatives As Selective Acetylcholinesterase Inhibitors”. Journal of Research in Pharmacy 30 (5): 1352-67. https://doi.org/10.12991/jrespharm.1897524.

EndNote

Ateş B, Dönmez F, Tan Uygun M (October 1, 2026) Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors. Journal of Research in Pharmacy 30 5 1352–1367.

IEEE

[1]B. Ateş, F. Dönmez, and M. Tan Uygun, “Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors”, J. Res. Pharm., vol. 30, no. 5, pp. 1352–1367, Oct. 2026, doi: 10.12991/jrespharm.1897524.

ISNAD

Ateş, Behiye - Dönmez, Fatih - Tan Uygun, Meltem. “Synthesis, Cholinesterase Inhibitory Activity, and in Silico Studies of Novel Pyrazolopyrazine Derivatives As Selective Acetylcholinesterase Inhibitors”. Journal of Research in Pharmacy 30/5 (October 1, 2026): 1352-1367. https://doi.org/10.12991/jrespharm.1897524.

JAMA

1.Ateş B, Dönmez F, Tan Uygun M. Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors. J. Res. Pharm. 2026;30:1352–1367.

MLA

Ateş, Behiye, et al. “Synthesis, Cholinesterase Inhibitory Activity, and in Silico Studies of Novel Pyrazolopyrazine Derivatives As Selective Acetylcholinesterase Inhibitors”. Journal of Research in Pharmacy, vol. 30, no. 5, Oct. 2026, pp. 1352-67, doi:10.12991/jrespharm.1897524.

Vancouver

1.Behiye Ateş, Fatih Dönmez, Meltem Tan Uygun. Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors. J. Res. Pharm. 2026 Oct. 1;30(5):1352-67. doi:10.12991/jrespharm.1897524