Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer's disease

Yerdelen K. O., KOCA M., ANIL B., Sevindik H., Kasap Z., HALICI Z., ...More

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.25, no.23, pp.5576-5582, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 23
  • Publication Date: 2015
  • Doi Number: 10.1016/j.bmcl.2015.10.051
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.5576-5582
  • Keywords: Donepezil, Amyloid beta, Alzheimer, AChE, BuChE, AMYLOID-BETA, ANTICHOLINESTERASE ACTIVITY, ACETYLCHOLINESTERASE, INHIBITORS, DOCKING, AGGREGATION, ANALOGS, ACHE, BUTYRYLCHOLINESTERASE, 2-BUTENEDIAMIDE
  • Erzincan Binali Yildirim University Affiliated: Yes

Abstract

Amyloid beta (A beta) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimer's disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and A beta with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and beta(1-42) inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimer's agents. (C) 2015 Elsevier Ltd. All rights reserved.