Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors

Tamás Kálai, Robin Altman, Izumi Maezawa, Mária Balog, Christophe Morisseau, Jitka Petrlova, Bruce D. Hammock, Lee-Way Jin, James R. Trudell, John C Voss, Kálmán Hideg

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A series of new Tacrine analogs modified with nitroxides or pre-nitroxides on 9-amino group via methylene or piperazine spacers were synthesized; the nitroxide or its precursors were incorporated into the Tacrine scaffold. The new compounds were tested for their hydroxyl radical and peroxyl radical scavenging ability, acetylcholinesterase inhibitor activity and protection against Aβ-induced cytotoxicity. Based on these assays, we conclude that Tacrine analogs connected to five and six-membered nitroxides via piperazine spacers (9b, 9b/HCl and 12) exhibited the best activity, providing direction for further development of additional candidates with dual functionality (anti Alzheimer's and antioxidant).

Original languageEnglish (US)
Pages (from-to)343-350
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume77
DOIs
StatePublished - Apr 22 2014

Keywords

  • Alzheimer's disease
  • Antioxidants
  • Nitroxides
  • Spin trapping
  • Tacrine

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors'. Together they form a unique fingerprint.

Cite this