Phenylpropanoids are secondary metabolites widely distributed in plants. They are believed to protect human cells against oxidative stress and in turn, to prevent various diseases associated with it, such as cancer, cardiovascular, and neurodegenerative disorders as well [2,3]. Recently, many natural phenylpropanoids have emerged as a particularly promising class of small molecules able to inhibit β-amyloid aggregation and disrupt preformed amyloid fibrils that represent important targets in the development of pharmacological treatments of Alzheimer’s disease (AD) [4]. Unfortunately, natural phenylpropanoids often have poor pharmacokinetic properties and low bioavailability. In this frame an interesting approach in the design of new bioactive compounds could be the combination of two or more polyphenolic "fragments". This "natural-fragment-based drug-discovery" approach would allow the assembly, also in a combinatorial manner, of libraries based on complex polyphenols in a few steps. This strategy provides us with the possibility of easily modifying both scaffold and decorations and modulating pharmacodynamic and pharmacokinetic properties [5]. Therefore, we planned to join two "tyrosol-fragments" by a phosphodiester bridge to obtain a new class of phosphate-linked compounds [6], which are potentially more bioactive than the corresponding precursors. We report here the general synthetic strategy to obtain new phosphate-linked tyrosol dimers in good yield and their full characterization. Since oxidative stress, as well as metal ion dyshomeostasis, are known to play important roles in AD pathogenesis, preliminary studies are focused on the evaluation of their antioxidant activity, metal chelating ability and their ability to inhibit β-amyloid aggregation.

New Phosphate-Linked Tyrosol Dimers: Synthesis, antioxidant activity, metal chelating capacity and effect on Aβ aggregation / Giordano, Maddalena; Romanucci, Valeria; Bernini, Roberta; Mariangela, Clemente; Sara, García-Viñuales; Danilo, Milardi; Iuliano, Mauro; DE TOMMASO, Gaetano; Zarrelli, Armando; DI FABIO, Giovanni. - (2019). (Intervento presentato al convegno XXXIX Convegno Nazionale della Divisione di Chimica Organica tenutosi a Torino (Italia) nel 8-12 settembre 2018).

New Phosphate-Linked Tyrosol Dimers: Synthesis, antioxidant activity, metal chelating capacity and effect on Aβ aggregation

Maddalena Giordano;Valeria Romanucci;BERNINI, ROBERTA;Mauro Iuliano;Gaetano De Tommaso;Armando Zarrelli;Giovanni Di Fabio
2019

Abstract

Phenylpropanoids are secondary metabolites widely distributed in plants. They are believed to protect human cells against oxidative stress and in turn, to prevent various diseases associated with it, such as cancer, cardiovascular, and neurodegenerative disorders as well [2,3]. Recently, many natural phenylpropanoids have emerged as a particularly promising class of small molecules able to inhibit β-amyloid aggregation and disrupt preformed amyloid fibrils that represent important targets in the development of pharmacological treatments of Alzheimer’s disease (AD) [4]. Unfortunately, natural phenylpropanoids often have poor pharmacokinetic properties and low bioavailability. In this frame an interesting approach in the design of new bioactive compounds could be the combination of two or more polyphenolic "fragments". This "natural-fragment-based drug-discovery" approach would allow the assembly, also in a combinatorial manner, of libraries based on complex polyphenols in a few steps. This strategy provides us with the possibility of easily modifying both scaffold and decorations and modulating pharmacodynamic and pharmacokinetic properties [5]. Therefore, we planned to join two "tyrosol-fragments" by a phosphodiester bridge to obtain a new class of phosphate-linked compounds [6], which are potentially more bioactive than the corresponding precursors. We report here the general synthetic strategy to obtain new phosphate-linked tyrosol dimers in good yield and their full characterization. Since oxidative stress, as well as metal ion dyshomeostasis, are known to play important roles in AD pathogenesis, preliminary studies are focused on the evaluation of their antioxidant activity, metal chelating ability and their ability to inhibit β-amyloid aggregation.
2019
New Phosphate-Linked Tyrosol Dimers: Synthesis, antioxidant activity, metal chelating capacity and effect on Aβ aggregation / Giordano, Maddalena; Romanucci, Valeria; Bernini, Roberta; Mariangela, Clemente; Sara, García-Viñuales; Danilo, Milardi; Iuliano, Mauro; DE TOMMASO, Gaetano; Zarrelli, Armando; DI FABIO, Giovanni. - (2019). (Intervento presentato al convegno XXXIX Convegno Nazionale della Divisione di Chimica Organica tenutosi a Torino (Italia) nel 8-12 settembre 2018).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/776944
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