Microwave-Assisted Synthesis, Molecular Docking, and Cholinesterase Inhibitory Activities of New Ethanediamide and 2-Butenediamide Analogues

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

CHEMICAL & PHARMACEUTICAL BULLETIN, cilt.63, sa.3, ss.210-217, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 63 Sayı: 3
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1248/cpb.c14-00754
  • Dergi Adı: CHEMICAL & PHARMACEUTICAL BULLETIN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.210-217
  • Anahtar Kelimeler: ethanediamide, 2-butenediamide, anticholinesterase activity, molecular docking, ALZHEIMERS-DISEASE, BIOLOGICAL EVALUATION, LIGAND INTERACTIONS, BUCHE INHIBITORS, SCORING FUNCTION, BUTYRYLCHOLINESTERASE, ACETYLCHOLINESTERASE, THERAPY, NEUROPROTECTION, DERIVATIVES
  • Atatürk Üniversitesi Adresli: Evet

Özet

A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives were synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The synthesized compounds were evaluated against ChE enzymes using the colorimetric method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among which compounds if and 2f were the most active inhibitors against BuChE (IC50 value=1.471 mu M) and AChE (IC50 value=2.099 mu M), respectively. Docking simulations revealed that the inhibitors if and 2f are capable of simultaneously binding the peripheral anionic site as well as the catalytic anionic site of both ChE enzymes. These derivatives are considered interesting candidates for Alzheimer's disease treatment.