Design and Synthesis of New Thiazole Derivatives for Alzheimer’s Disease Therapy as a Potential Cholinesterase Inhibitor; Toxicity Prediction and Molecular Docking Studies and Biological Evaluation
9 affiliations
- 1Department of Bioengineering, Faculty of Engineering, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey
- 2Faculty of Pharmacy, University for Business and Technology, 60000 Prishtina, Kosovo
- 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bulent Ecevit University, 67600 Zonguldak, Turkey
- 4Department of Pharmaceutical Chemistry, Graduate School, Anadolu University, 26470 Eskisehir, Turkey
- 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
- 6Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
- 7Department of Biotechnology, Graduate Education Institute, Bilecik Seyh Edebali University, 11230 Bilecik, Turkey
- 8Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey
- 9The Rectorate of Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey
Abstract
In this study, thiazole derivatives 13–23 were synthesized as novel cholinesterase inhibitors. Their structures were elucidated using 1H-NMR, 13C-NMR, and elemental analysis techniques. The binding positions and efficiencies of the designed compounds on the enzyme were investigated through molecular docking studies, and the properties of ADMET were examined using computational methods. Cytotoxicity analyses of the synthesized compounds were performed to screen their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. It has been determined that these compounds do not exhibit a significant cytotoxic effect on healthy endothelial cells. Although the compounds showed lower efficacy in AChE inhibition compared to the reference compound tacrine (IC50: 0.136 μM; KI: 0.46 ± 0.01 nM), they exhibited moderate inhibitory effects. Among these, compounds 16 and 23 were found to be the most potent AChE inhibitors, with IC50 values of 36.47 µM and 34.65 µM, and KI values of 22.20 ± 1.23 and 21.10 ± 1.58 µM, respectively, while compounds 15 and 20 were found to be the most potent BChE inhibitors, with IC50 values of 17.76 µM and 16.90 µM, and KI values of 14.10 ± 0.58 and 13.40 ± 0.48 µM, respectively, on other cholinesterases. These tested compounds can be considered potential candidates for further research in the treatment of Alzheimer’s disease (AD).
Related
- Design, Synthesis, and Biological Evaluation of Molecular Hybrids Incorporating Coumarin-Pyrazole-Linked Indolinone Derivatives With Antioxidant and Anti-Alzheimer Properties.
- 3H-1,5-Benzodiazepine Derivatives as Novel Antimalarial Agents: Synthesis, Biological Evaluation and Computational Target Exploration
- Design, synthesis, and biological evaluation of naphthalimide derivatives as dual monoamine oxidase-B and amyloid-β aggregation inhibitors for Alzheimer's disease.
- Design, synthesis and biological evaluation of novel artemisinin derivatives as potent P-glycoprotein modulators for overcoming multidrug resistance.
- Synthesis and biological evaluation of pyridine-based derivatives as potential inhibitors of Leishmania major propagation.
BibTeX
@article{isık2026design,
title = {{Design and Synthesis of New Thiazole Derivatives for Alzheimer’s Disease Therapy as a Potential Cholinesterase Inhibitor; Toxicity Prediction and Molecular Docking Studies and Biological Evaluation}},
author = {Mesut Işık and Gresa Halimi Syla and Abdüllatif Karakaya and Ulviye Acar Çevik and Nour El-Huda Daoud and Muhammet Fırat and Yüksel Öğünç Keçeci and Yusuf Özkay and Zafer Asım Kaplancıklı and Şükrü Beydemir},
journal = {Molecules (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/molecules31193568},
url = {https://europepmc.org/article/PMC/PMC13666930},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design and Synthesis of New Thiazole Derivatives for Alzheimer’s Disease Therapy as a Potential Cholinesterase Inhibitor; Toxicity Prediction and Molecular Docking Studies and Biological Evaluation
AU - Mesut Işık
AU - Gresa Halimi Syla
AU - Abdüllatif Karakaya
AU - Ulviye Acar Çevik
AU - Nour El-Huda Daoud
AU - Muhammet Fırat
AU - Yüksel Öğünç Keçeci
AU - Yusuf Özkay
AU - Zafer Asım Kaplancıklı
AU - Şükrü Beydemir
PY - 2026
DA - 2026/10/01
JO - Molecules (Basel, Switzerland)
DO - 10.3390/molecules31193568
UR - https://europepmc.org/article/PMC/PMC13666930
AB - In this study, thiazole derivatives 13–23 were synthesized as novel cholinesterase inhibitors. Their structures were elucidated using 1H-NMR, 13C-NMR, and elemental analysis techniques. The binding positions and efficiencies of the designed compounds on the enzyme were investigated through molecular docking studies, and the properties of ADMET were examined using computational methods. Cytotoxicity analyses of the synthesized compounds were performed to screen their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. It has been determined that these compounds do not exhibit a significant cytotoxic effect on healthy endothelial cells. Although the compounds showed lower efficacy in AChE inhibition compared to the reference compound tacrine (IC50: 0.136 μM; KI: 0.46 ± 0.01 nM), they exhibited moderate inhibitory effects. Among these, compounds 16 and 23 were found to be the most potent AChE inhibitors, with IC50 values of 36.47 µM and 34.65 µM, and KI values of 22.20 ± 1.23 and 21.10 ± 1.58 µM, respectively, while compounds 15 and 20 were found to be the most potent BChE inhibitors, with IC50 values of 17.76 µM and 16.90 µM, and KI values of 14.10 ± 0.58 and 13.40 ± 0.48 µM, respectively, on other cholinesterases. These tested compounds can be considered potential candidates for further research in the treatment of Alzheimer’s disease (AD).
SN - 1420-3049
ER -