Synthesis of New Tyrosol‐Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability. (26th January 2021)

• Record Type: Journal Article
• Authors: Romanucci, Valeria; Giordano, Maddalena; De Tommaso, Gaetano; Iuliano, Mauro; Bernini, Roberta; Clemente, Mariangela; Garcia‐Viñuales, Sara; Milardi, Danilo; Zarrelli, Armando; Di Fabio, Giovanni
• Is Part Of: ChemMedChem. Volume 16:Number 7(2021)
• Page Start: 1172
• Page End: 1183
• Publication Date: 2021-01-26
• Subjects: Alzheimer's disease -- amyloid aggregation -- amyloid beta-peptides -- dimer flavonoids -- hydroxytyrosol; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000807
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modulation might have a positive and synergic effect in contrasting AD‐related impairments. Herein, a new and efficient fragment‐based approach towards tyrosol phosphodiester derivatives (TPDs) has been developed starting from suitable tyrosol building blocks and exploiting the well‐established phosphoramidite chemistry. The antioxidant activity of new TPDs has been tested as well as their ability to inhibit Aβ protein aggregation. In addition, their metal chelating ability has been evaluated as a possible strategy to develop new natural‐based entities for the prevention or therapy of AD. Interestingly, TPDs containing a catechol moiety have demonstrated highly promising activity in inhibiting the aggregation of Aβ40 and a strong ability to chelate biometals such as Cu II and Zn II . Abstract : Efficient fragments : Phosphoramidite chemistry leads to new compounds containing two tyrosol fragments linked through a phosphodiester bond. Interesting Aβ anti‐aggregating activities were found as well as an excellent ability to chelate biometals like Cu II and Zn II, whose regulation plays a key role in neurodegeneration processes.