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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 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).

SUBMITTER: Kalai T

PROVIDER: S-EPMC4065883 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Kálai Tamás T Altman Robin R Maezawa Izumi I Balog Mária M Morisseau Christophe C Petrlova Jitka J Hammock Bruce D BD Jin Lee-Way LW Trudell James R JR Voss John C JC Hideg Kálmán K

European journal of medicinal chemistry 20140312

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 n ...[more]

PMID: 24657571

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