Synthesis, molecular modeling and evaluation of novel N '-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and A beta aggregation

Ozer E. O., TAN O., Ozadali K., KUCUKKILINC T., BALKAN A., UÇAR G.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.23, no.2, pp.440-443, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 2
  • Publication Date: 2013
  • Doi Number: 10.1016/j.bmcl.2012.11.064
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.440-443
  • Keywords: Alzheimer's disease, Cholinesterase, Beta-amyloid fibril, N-Acylhydrazone, Molecular modeling, ALZHEIMERS-DISEASE, ACETYLCHOLINESTERASE INHIBITORS, HYPOTHESIS, TORPEDO, BINDING, HYBRIDS, DESIGN, MUTANT, DRUGS, VENOM
  • Hacettepe University Affiliated: Yes


To develop new drugs for treatment of Alzheimer's disease, a group of N'-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase and aggregation of amyloid beta peptides (1-40, 1-42 and 1-40_ 1-42). The enzyme inhibition assay results indicated that compounds moderately inhibit both acetylcholinesterase and butyrylcholinesterase. beta-Amyloid aggregation results showed that all compounds exhibited remarkable A beta fibril aggregation inhibition activity with a nearly similar potential as the reference compound rifampicin, which makes them promising anti-Alzheimer drug candidates. Docking experiments were carried out with the aim to understand the interactions of the most active compounds with the active site of the cholinesterase enzymes. (C) 2012 Elsevier Ltd. All rights reserved.