Mitoxantrone analogues as ligands for a stem-loop structure of tau pre-mRNA.

Yang Liu, Eleanor Peacey, John Dickson, Christine P Donahue, Suxin Zheng, Gabriele Varani, Michael S Wolfe

Index: J. Med. Chem. 52 , 6523-6, (2009)

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Abstract

A series of mitoxantrone (MTX) analogues have been designed, synthesized, and evaluated for binding to and stabilizing a stem-loop structure that serves as a splicing regulatory element in the pre-mRNA of tau, which is involved in Alzheimer's and other neurodegenerative diseases. Several compounds showed significantly improved binding activity relative to the original screening hit mitoxantrone. These findings establish essential structure-activity relationships to further optimize the activity of this promising class of compounds.