Synthesis of p-coumarates with potential anti-Alzheimer's action: Enzyme inhibition and in silico studies


Pereira Lopes S., Emídio J. J., Sucupira Duarte A. B., Erdoğan Orhan ., Şenol Deniz F. S., Salmas R. E., ...Daha Fazla

CHEMISTRY AND BIODIVERSITY, cilt.1, sa.1, ss.1-12, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1 Sayı: 1
  • Basım Tarihi: 2026
  • Dergi Adı: CHEMISTRY AND BIODIVERSITY
  • Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1-12
  • Lokman Hekim 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 twenty-two 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 µM. The structures of the synthesized compounds were characterized by FTIR, 1H-NMR, 13C-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.

Keywords: natural product, cholinesterase inhibitors, acetylcholinesterase, butyrylcholinesterase, Alzheimer’s disease.