Synthesis of New Tyrosol-Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability

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 beta (A beta) 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 A beta 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 A beta(40) and a strong ability to chelate biometals such as Cu-II and Zn-II.

Automated summary

Alzheimer's disease is a multifactorial pathology involving amyloid beta aggregation and oxidative stress. A new study has developed tyrosol phosphodiester derivatives (TPDs) with antioxidant properties and the ability to inhibit Aβ protein aggregation. TPDs containing a catechol moiety showed promising activity in inhibiting Aβ aggregation and chelating biometals.