Synthesis of <i>p</i>-Coumarates With Potential Anti-Alzheimer's Action: Enzyme Inhibition and In Silico Studies


Lopes S. P., Emídio J. J., Duarte A. B. S., ERDOĞAN ORHAN ., Deniz F. S., Salmas R. E., ...Daha Fazla

CHEMISTRY & BIODIVERSITY, cilt.23, sa.4, 2026 (SCI-Expanded, Scopus) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 4
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1002/cbdv.202503857
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
  • Anahtar Kelimeler: acetylcholinesterase, Alzheimer's disease, butyrylcholinesterase, cholinesterase inhibitors, natural product
  • Gazi Üniversitesi Adresli: Evet

Özet

Alzheimer's disease (AD) is a fatal neurodegenerative disorder that affects cognition, memory, and behavior. Such a disease is considered the most common cause of dementia and affects a large portion of the elderly population worldwide. Currently, cholinesterase inhibitors are used to reduce the symptoms and rate of progression of this disease. Thus, the present study evaluated the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of a set of 22 p-coumarate derivatives using the spectrophotometric method. The inhibitory activity of the compounds against AChE and BChE was measured using the adapted Ellman spectrophotometric method; the reported inhibition percentages were determined at a final concentration of 100 & micro;M. The structures of the synthesized compounds were characterized by FTIR, H-1-NMR, C-13-NMR, and HRMS spectroscopy. Among the compounds tested, three showed moderate inhibitory activity against AChE and good activity against BChE: (E)-4-chlorobenzyl 3-(4-hydroxyphenyl)acrylate (14) (56.36%; 75.17%), (E)-4-bromobenzyl 3-(4-hydroxyphenyl)acrylate (15) (61.11%; 76.09%), and (E)-naphthalene 3-(4-hydroxyphenyl)acrylate (18) (59.18%; 65.39%), respectively. Compound 15 had an IC50 of 22.22 +/- 1.50 mM against BChE, which is notably better than galantamine's BChE inhibition. The in silico analysis suggested that compounds 14, 15, and 18 interact with AChE and BChE. Thus, p-coumaric acid derivatives represent promising prototypes for the search for new drug candidates for the treatment of AD.