Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.

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Rizzo S, Bisi A, Bartolini M, Mancini F, Belluti F, Gobbi S, Andrisano V, Rampa A

Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.

Eur J Med Chem. 2011 Sep;46(9):4336-43. doi: 10.1016/j.ejmech.2011.07.004. Epub 2011 Jul 8.

PubMed ID

21798635 [ View in PubMed

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Abstract

The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the development of a broad collection of very interesting homo- and heterodimeric structures, conceived in light of the emerging multi-target approach for AD-related drug discovery. As a contribution to the topic, we report here the design, synthesis and biological evaluation of 12 compounds referable to bis(7)-tacrine. In addition to the cholinesterase activity, some of the selected compounds (7-9 and 12) were capable of inhibiting the non-enzymatic function of AChE and/or showed a remarkable activity against BACE1. Thus, the present study outlines a series of newly synthesized molecules, structurally related to bis(7)-tacrine, endowed with extended biological profile in agreement with the emerging multi-target paradigm.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Tacrine	Acetylcholinesterase	IC 50 (nM)	250	N/A	N/A	Details