1. Multi-target strategy to address Alzheimer’s disease: Design, synthesis and biological evaluation of new tacrine-based dimers
- Author
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Rizzo, Stefano, Bisi, Alessandra, Bartolini, Manuela, Mancini, Francesca, Belluti, Federica, Gobbi, Silvia, Andrisano, Vincenza, and Rampa, Angela
- Subjects
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ORGANIC synthesis , *TARGETED drug delivery , *ALZHEIMER'S disease , *DRUG design , *DIMERS , *PHARMACEUTICAL research , *CHOLINESTERASES , *ENZYME kinetics , *QUINOLINE - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2011
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