N-Substituted Arylidene-3-(Methylsulfonyl)-2-Oxoimidazolidine-1-Carbohydrazide as Cholinesterase Inhibitors: Design, Synthesis, and Molecular Docking Study

TOK F., SAĞLIK B. N., ÖZKAY Y., KAPLANCIKLI Z. A., KAYMAKÇIOĞLU B.

CHEMISTRY & BIODIVERSITY, cilt.19, sa.8, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 8
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/cbdv.202200265
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Alzheimer's disease, beta-amyloid plaque, hydrazone, imidazolidine ring, molecular modeling, BIOLOGICAL EVALUATION, DERIVATIVES BEARING, ANALOGS, MOIETY
  • Marmara Üniversitesi Adresli: Evet

Özet

The development of new enzyme inhibitors in degenerative brain diseases has gained more attention. Enzyme inhibitors play an effective role in controlling central nervous system diseases. For this purpose, a novel series of hydrazone derivatives containing imidazolidine ring aimed against Alzheimer's disease (AD), have been designed and synthesized. The acetylcholinesterase (AChE) enzyme inhibitory activity of these compounds was investigated. The structures of the compounds were determined by IR, H-1 and C-13-NMR and mass spectroscopic methods. Inhibition studies on the cholinesterase (ChE) enzymes and beta-amyloid plaque inhibition test of the compounds were performed. Based on the experimental results, compound 3j bearing dimethoxy substituent on the aromatic ring like donepezil exhibited the most AChE inhibitory activity with the IC50 values of 0.023 +/- 0.001 mu M. Owing to obtained biological activity and molecular docking study results, it is thought that the most active compound 3j may play a role in both symptomatic and palliative treatment of AD.