2. Academic Validation
  3. Design, Synthesis, and Molecular Docking Studies of Novel Pyrazoline-Thiazoles as Cholinesterase Dual-Target Inhibitors for the Treatment of Alzheimer's Disease

Design, Synthesis, and Molecular Docking Studies of Novel Pyrazoline-Thiazoles as Cholinesterase Dual-Target Inhibitors for the Treatment of Alzheimer's Disease

  • ACS Omega. 2025 Aug 22;10(34):38427-38439. doi: 10.1021/acsomega.5c01055.
Betül Kaya 1,  Ulviye Acar Çevik 2 3,  Bilge Çiftçi 4,  Adem Necip 5,  Mesut Işik 6,  Ebru Nur Ay 7,  Süleyman Yur 3,  Yusuf Özkay 2,  Şükrü Beydemir 8,  Zafer Asım Kaplancıklı 2 9
Affiliations

Affiliations

  • 1 Vocational School of Health Services, Pharmacy Services, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 3 Medicinal Plant, Drug and Scientific Research and Application Center (AUBIBAM), Anadolu University, 26470 Eskişehir, Turkey.
  • 4 Vocational School of Health Services, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
  • 5 Vocational School of Health Services, Pharmacy Services, Harran University, 63300 Şanlıurfa, Turkey.
  • 6 Department of Bioengineering, Faculty of Engineering, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
  • 7 Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, İstinye University, 34396 İstanbul, Turkey.
  • 8 Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 9 The Rectorate of Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
PMID: 40918343 DOI: 10.1021/acsomega.5c01055
Abstract

Ten novel pyrazoline-thiazole derivatives were synthesized and assessed for their potential as acetylcholinesterase and butyrylcholinesterase inhibitors. The structure of the target compounds was characterized by 1H NMR and 13C NMR, and purity was determined using HPLC. The in vitro enzyme inhibitory activity assays determined that compounds 3f (IC50 = 0.382 μM) and 3g (IC50 = 0.338 μM) showed good inhibitory activity of acetylcholinesterase (AChE). Compound 3f has a selective inhibitory effect on AChE, while compound 3g has a dual effect, being effective against both AChE and BChE (IC50 = 2.087 μM). The molecular docking results of compound 3g with high inhibitory activity for AChE experimentally showed that it has a strong inhibitory effect close to that of the reference inhibitor tacrine. The compound 3g was found to have the highest activity in its interaction with the BChE (4BDS) protein with a low docking score (-5.555 kcal/mol). Furthermore, the prediction of ADME properties of compounds 3f and 3g was determined through Swiss ADME.

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