Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies

ÇAVDAR H., ŞENTÜRK M., GÜNEY M., DURDAĞI S., Kayik G., Supuran C. T., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.34, sa.1, ss.429-437, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 1
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1080/14756366.2018.1543288
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.429-437
  • Anahtar Kelimeler: Alzheimer's disease, uracil derivatives, acetylcholinesterase, butyrylcholinesterase, inhibitor, docking, MD simulations, CARBONIC-ANHYDRASE INHIBITORS, CHOLINESTERASE-INHIBITORS, BIOLOGICAL EVALUATION, IN-SILICO, TACRINE DERIVATIVES, ALZHEIMERS-DISEASE, MOLECULAR DOCKING, CINNAMIC ACID, ISOZYME-II, DESIGN
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer's disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives. The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Molecular docking and molecular dynamics (MD) simulations demonstrated the possible key interactions between the studied ligands and amino acid residues at different regions of the active sites of AChE and BuChE. Being diverse of the classical AChE and BuChE inhibitors, the investigated uracil derivatives may be used as lead molecules for designing new therapeutically effective enzyme inhibitors.