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 BACE 1. 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.
S. Rizzo, A. Bisi, M. Bartolini, F. Mancini, F. Belluti, S. Gobbi, et al. (2011). Multi-target strategy to address Alzheimer’s disease: Design, synthesis and biological evaluation of new tacrine-based dimers. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 46, 4336-4343 [10.1016/j.ejmech.2011.07.004].
Multi-target strategy to address Alzheimer’s disease: Design, synthesis and biological evaluation of new tacrine-based dimers
BISI, ALESSANDRA;BARTOLINI, MANUELA;MANCINI, FRANCESCA;BELLUTI, FEDERICA;GOBBI, SILVIA;ANDRISANO, VINCENZA;RAMPA, ANGELA
2011
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 BACE 1. 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
