Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer's disease agents

William Horton, Abha Sood, Swarada Peerannawar, Nandor Kugyela, Aditya Kulkarni, Rekha Tulsan, Chris D. Tran, Jessica Soule, Harry LeVine, Béla Török, Marianna Török

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies.

Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number2
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Antioxidant
  • Cholinesterase inhibition
  • β-Carbolines

ASJC Scopus subject areas

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

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