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

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).

DOI: 10.1016/j.ejmech.2014.03.026

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Cite this paper

@article{Kli2014SynthesisAF, title={Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors.}, author={T{\'a}m{\'a}s K{\'a}l{\'a}i and R. F. A. Altman and Izumi Maezawa and M{\'a}ria Balog and Christophe H P Morisseau and Jitka Petrlova and Bruce D Hammock and Lee-way Jin and James R. Trudell and John Voss and K{\'a}lm{\'a}n Hideg}, journal={European journal of medicinal chemistry}, year={2014}, volume={77}, pages={343-50} }