Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease

Maria Laura Bolognesi, Rita Banzi, Manuela Bartolini, Andrea Cavalli, Andrea Tarozzi, Vincenza Andrisano, Anna Minarini, Michela Rosini, Vincenzo Tumiatti, Christian Bergamini, Romana Fato, Giorgio Lenaz, Patrizia Hrelia, Antonino Cattaneo, Maurizio Recanatini, Carlo Melchiorre

Research output: Contribution to journalArticlepeer-review

Abstract

One of the characteristics of Alzheimer's disease (AD) that hinders the discovery of effective disease-modifying therapies is the multifactorial nature of its etiopathology. To circumvent this drawback, the use of multi-target-directed ligands (MTDLs) has recently been proposed as a means of simultaneously hitting several targets involved in the development of the AD syndrome. In this paper, a new class of MTDLs based on a polyamine - quinone skeleton, whose lead (memoquin, 2) showed promising properties in preclinical investigations (Cavalli et al. Angew. Chem., Int. Ed. 2007, 46, 3689-3692), is described. 3-29 were tested in vitro against a number of isolated AD-related targets, namely, AChE and BChE, and Aβ aggregation (both AChE-mediated and self-induced). Furthermore, the ability of the compounds to counteract the oxidative stress in a human neuronal-like cellular system (SH-SY5Y cells) was assayed, in both the presence and absence of NQO1, an enzyme able to generate and maintain the reduced form of quinone.

Original languageEnglish
Pages (from-to)4882-4897
Number of pages16
JournalJournal of Medicinal Chemistry
Volume50
Issue number20
DOIs
Publication statusPublished - Oct 20 2007

ASJC Scopus subject areas

  • Organic Chemistry

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