Novel Aminothiazole–Chalcone Analogs: Synthesis, Evaluation Acetylcholinesterase Activity, In Silico Analysis

Keçeci Sarıkaya M., Yıldırım Ş., KOÇYİĞİT Ü. M., Ceylan M., Yırtıcı Ü., Eyüpoğlu V.

Chemistry and Biodiversity, cilt.22, sa.5, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 5
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/cbdv.202402777
  • Dergi Adı: Chemistry and Biodiversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: acetylcholinesterase, ADME prediction, aminothiazole–chalcone, molecular docking, molecular dynamics
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

In this study, novel thiazole–chalcone analogs were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) were examined. In vitro enzyme activity studies were conducted to calculate IC50 values, which were found to range between 2.55 and 72.78 µM (tacrine IC50 = 53.31 µM). The Ki values of the compounds showing the best inhibition (6g and 6e) were calculated and compared to those of the standard substance tacrine. All compounds reduced the AChE activity. Additionally, predictions made with SwissADME indicated that all compounds complied with Lipinski's rules and possessed good oral bioavailability properties, and the inhibitory effects of compounds 6e and 6g on AChE were evaluated using molecular docking and molecular dynamics simulations (100 ns). The results showed that compounds 6e and 6g had strong and stable interactions with AChE.