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

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11 Citations (Scopus)

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
Pages (from-to)343-350
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume77
DOIs
Publication statusPublished - Apr 22 2014

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Kálai, T., Altman, R., Maezawa, I., Balog, M., Morisseau, C., Petrlova, J., Hammock, B. D., Jin, L. W., Trudell, J. R., Voss, J. C., & Hideg, K. (2014). Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors. European Journal of Medicinal Chemistry, 77, 343-350. https://doi.org/10.1016/j.ejmech.2014.03.026