Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives

Hasan Erdinç Sellitepe; Ahmet Buğra Aksel; Didem Akkaya; Arzu Özel

doi:10.17776/csj.1916608

Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives

Abstract

The design of dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a highly significant strategy in the treatment of Alzheimer’s disease. In this study, six new thiosemicarbazone-carbamate derivatives (8a-c, 9a-c) were designed and synthesized, based on vanillin and isovanillin, as potential dual inhibitors of cholinesterases for the treatment of Alzheimer’s disease. In vitro biological activity assessments revealed that the synthesized compounds had greater potential to inhibit BChE than AChE. Compound 8a, which emerged as the most potent BChE inhibitor in the series, exhibited 81.49% inhibition at 100 µM and an IC₅₀ of 58.41 µM, inhibiting the enzyme via a non-competitive mechanism, whilst compound 9c exhibited the highest AChE inhibition at the same concentration, with a rate of 40.27%. Molecular docking simulations supported the biological findings by confirming that the active compounds form hydrogen bonds and π-π interactions with critical amino acids in the catalytic sites of both enzymes. Furthermore, the in silico pharmacokinetic analyses conducted revealed that all derivatives possess a drug-like profile and exhibit high blood-brain barrier permeability scores (4.00–4.01), indicating their potential to reach the central nervous system.

Keywords

Alzheimer's disease, Carbamate, Cholinesterase inhibitor, Thiosemicarbazone

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Hasan Erdinç Sellitepe ^*
0000-0001-5339-6940
Türkiye

Ahmet Buğra Aksel
0000-0001-5090-6474
Türkiye

Didem Akkaya
0000-0002-0711-951X
Türkiye

Arzu Özel
0000-0001-7381-5575
Türkiye

Publication Date

August 31, 2026

Submission Date

April 3, 2026

Acceptance Date

August 5, 2026

Published in Issue

Year 2026 Volume: 47 Number: 4

DOI

https://doi.org/10.17776/csj.1916608

IZ

https://izlik.org/JA76AE46XF

APA

Sellitepe, H. E., Aksel, A. B., Akkaya, D., & Özel, A. (2026). Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives. Cumhuriyet Science Journal, 47(4), 729-738. https://doi.org/10.17776/csj.1916608

AMA

1.Sellitepe HE, Aksel AB, Akkaya D, Özel A. Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives. CSJ. 2026;47(4):729-738. doi:10.17776/csj.1916608

Chicago

Sellitepe, Hasan Erdinç, Ahmet Buğra Aksel, Didem Akkaya, and Arzu Özel. 2026. “Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives”. Cumhuriyet Science Journal 47 (4): 729-38. https://doi.org/10.17776/csj.1916608.

EndNote

Sellitepe HE, Aksel AB, Akkaya D, Özel A (August 1, 2026) Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives. Cumhuriyet Science Journal 47 4 729–738.

IEEE

[1]H. E. Sellitepe, A. B. Aksel, D. Akkaya, and A. Özel, “Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives”, CSJ, vol. 47, no. 4, pp. 729–738, Aug. 2026, doi: 10.17776/csj.1916608.

ISNAD

Sellitepe, Hasan Erdinç - Aksel, Ahmet Buğra - Akkaya, Didem - Özel, Arzu. “Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives”. Cumhuriyet Science Journal 47/4 (August 1, 2026): 729-738. https://doi.org/10.17776/csj.1916608.

JAMA

1.Sellitepe HE, Aksel AB, Akkaya D, Özel A. Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives. CSJ. 2026;47:729–738.

MLA

Sellitepe, Hasan Erdinç, et al. “Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives”. Cumhuriyet Science Journal, vol. 47, no. 4, Aug. 2026, pp. 729-38, doi:10.17776/csj.1916608.

Vancouver

1.Hasan Erdinç Sellitepe, Ahmet Buğra Aksel, Didem Akkaya, Arzu Özel. Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives. CSJ. 2026 Aug. 1;47(4):729-38. doi:10.17776/csj.1916608

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

Targeting Cholinesterases: Synthesis of Novel Thiosemicarbazone-Carbamate Derivatives

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