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

Kálai, Tamás and Altman, Robin and Maezawa, Izumi and Balog, Mária and Morisseau, Christophe and Petrolva, Jitka and Hammock, Bruce D. and Jin, Lee-Way and Trudell, James R. and Voss, John C. and Hideg, Kálmán (2014) Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 77. pp. 343-350. ISSN 0223-5234

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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, acetyl cholinesterase inhibitor activity and protection against A-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).

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