Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease

Seema Bag, Sanjukta Ghosh, Rekha Tulsan, Abha Sood, Weihong Zhou, Christine Schifone, Michelle Foster, Harry Levine, Béla Török, Marianna Török

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.

Original languageEnglish
Pages (from-to)2614-2618
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number9
DOIs
StatePublished - May 1 2013

Bibliographical note

Funding Information:
Financial support provided by the University of Massachusetts Boston, and National Institute of Health ( R-15 AG025777-03A1 and R21AG028816-01 to H.L.) is gratefully acknowledged.

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Chalcones
  • Cholinesterase inhibition
  • Coumarins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease'. Together they form a unique fingerprint.

Cite this