Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives

Yerdelen K. Ö., KOCA M., KASAP Z., ANIL B.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.30, sa.4, ss.671-678, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 4
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/14756366.2014.959947
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.671-678
  • Anahtar Kelimeler: 2-butenediamide, Alzheimer, metal chelation, molecular modelling, oxalamide, ALZHEIMERS-DISEASE, BUTYRYLCHOLINESTERASE INHIBITION, BIOLOGICAL EVALUATION, ACETYLCHOLINESTERASE, BETA, VARIANTS, THERAPY
  • Atatürk Üniversitesi Adresli: Evet

Özet

Several new oxalamide and 2-butenediamide derivatives have been designed, synthesized and evaluated as the acetyl- and butyryl-cholinesterase inhibitors for Alzheimer's disease. The enzyme inhibitory activity of the synthesized compounds was measured using Ellman's colorimetric method. It was revealed that compound 1a (N, N'-bis-(4-chloro-benzyl)-N, N'-diphenyl-oxalamide) showed maximum activity against BuChE with a half maximal inhibitory concentration (IC50) = 1.86 mu M and compound 2a (but-2-enedioic acid bis-[(4-chloro-benzyl)-phenyl-amide]) exhibited optimum AChE (IC50 = 1.51 mu M) inhibition with a high-selectivity index. To better understand the enzyme-inhibitor interaction of the most active compounds towards cholinesterase, molecular modelling studies were carried out. Docking simulations revealed that inhibitors 1a and 2a targeted both the catalytic active site and the peripheral anionic site of 1ACJ and 1P0I.