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

KAYA B., Çevik U. A., ÇİFTCİ B., Necip A., IŞIK M., Ay E. N., ...Daha Fazla

ACS Omega, cilt.10, sa.34, ss.38427-38439, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 34
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1021/acsomega.5c01055
  • Dergi Adı: ACS Omega
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Sayfa Sayıları: ss.38427-38439
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

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 by1H NMR and13C 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.