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. U. , Ozadali K. , KUCUKKILINC T., BALKAN A. , UÇAR G.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, cilt.23, ss.440-443, 2013 (SCI İndekslerine Giren Dergi) identifier

  • Cilt numarası: 23 Konu: 2
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.bmcl.2012.11.064
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Sayfa Sayıları: ss.440-443

Özet

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.