Polyamine Conjugation as a Promising Strategy To Target Amyloid Aggregation in the Framework of Alzheimer's Disease

Elena Simoni, Roberta Caporaso, Christian Bergamini, Jessica Fiori, Romana Fato, Przemyslaw Miszta, Sławomir Filipek, Filippo Caraci, Maria Laura Giuffrida, Vincenza Andrisano, Anna Minarini, Manuela Bartolini, Michela Rosini

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Abstract

Spermine conjugates 2-6, carrying variously decorated 3,5-dibenzylidenepiperidin-4-one as bioactive motives, were designed to direct antiaggregating properties into mitochondria, using a polyamine functionality as the vehicle tool. The study confirmed mitochondrial import of the catechol derivative 2, which displayed effective antiaggregating activity and neuroprotective effects against Aβ-induced toxicity. Notably, a key functional role for the polyamine motif in Aβ molecular recognition was also unraveled. This experimental readout, which was supported by in silico studies, gives important new insight into the polyamine's action. Hence, we propose polyamine conjugation as a promising strategy for the development of neuroprotectant leads that may contribute to decipher the complex picture of Aβ toxicity.

Original languageEnglish
Pages (from-to)1145-1150
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 8 2016

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Simoni, E., Caporaso, R., Bergamini, C., Fiori, J., Fato, R., Miszta, P., Filipek, S., Caraci, F., Giuffrida, M. L., Andrisano, V., Minarini, A., Bartolini, M., & Rosini, M. (2016). Polyamine Conjugation as a Promising Strategy To Target Amyloid Aggregation in the Framework of Alzheimer's Disease. ACS Medicinal Chemistry Letters, 7(12), 1145-1150. https://doi.org/10.1021/acsmedchemlett.6b00339