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Synthesis of New Tyrosol‐Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability
Author(s) -
Romanucci Valeria,
Giordano Maddalena,
De Tommaso Gaetano,
Iuliano Mauro,
Bernini Roberta,
Clemente Mariangela,
GarciaViñuales Sara,
Milardi Danilo,
Zarrelli Armando,
Di Fabio Giovanni
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000807
Subject(s) - tyrosol , phosphodiester bond , moiety , chemistry , chelation , amyloid (mycology) , antioxidant , catechol , amyloid β , β amyloid , oxidative stress , combinatorial chemistry , biochemistry , stereochemistry , alzheimer's disease , organic chemistry , disease , medicine , gene , inorganic chemistry , rna , pathology
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 Aβ 40 and a strong ability to chelate biometals such as Cu II and Zn II .