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 journalArticle

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

Fingerprint

Tacrine
Cholinesterase Inhibitors
Scavenging
Cytotoxicity
Scaffolds
Hydroxyl Radical
Assays
Antioxidants
Surveys and Questionnaires
piperazine

Keywords

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

ASJC Scopus subject areas

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

Cite this

Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors. / Kálai, Tamás; Altman, Robin; Maezawa, Izumi; Balog, Mária; Morisseau, Christophe; Petrlova, Jitka; Hammock, Bruce D.; Jin, Lee-Way; Trudell, James R.; Voss, John C; Hideg, Kálmán.

In: European Journal of Medicinal Chemistry, Vol. 77, 22.04.2014, p. 343-350.

Research output: Contribution to journalArticle

Kálai, Tamás ; Altman, Robin ; Maezawa, Izumi ; Balog, Mária ; Morisseau, Christophe ; Petrlova, Jitka ; Hammock, Bruce D. ; Jin, Lee-Way ; Trudell, James R. ; Voss, John C ; Hideg, Kálmán. / Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 77. pp. 343-350.
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AU - Hammock, Bruce D.

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