The study of compounds able to interfere in various ways with amyloid aggregation is of paramount importance in amyloid research. Molecules characterized by a 4-thiaflavane skeleton have received great attention in chemical, medicinal, and pharmaceutical research. Such molecules, especially polyhydroxylated 4-thiaflavanes, can be considered as structural mimickers of several natural polyphenols that have been previously demonstrated to bind and impair amyloid fibril formation. In this work, we tested five different 4-thiaflavanes on the hen egg-white lysozyme (HEWL) amyloid model for their potential anti-amyloid properties. By combining a thioflavin T assay, atomic force microscopy, and a cell toxicity assay, we demonstrated that such compounds can impair the formation of high-order amyloid aggregates and mature fibrils. Despite this, the tested 4-thiaflavanes, although non-toxic per se, are not able to prevent amyloid toxicity on human neuroblastoma cells. Rather, they proved to block early aggregates in a stable, toxic conformation. Accordingly, 4-thiaflavanes can be proposed for further studies aimed at identifying blocking agents for the study of toxicity mechanisms of amyloid aggregation.

Catechol-Containing Hydroxylated Biomimetic 4-Thiaflavanes as Inhibitors of Amyloid Aggregation / Ramazzotti, Matteo; Paoli, Paolo; Tiribilli, Bruno; Viglianisi, Caterina; Menichetti, Stefano; Degl’Innocenti, Donatella. - In: BIOMIMETICS. - ISSN 2313-7673. - ELETTRONICO. - 2:(2017), pp. 6-17. [10.3390/biomimetics2020006]

Catechol-Containing Hydroxylated Biomimetic 4-Thiaflavanes as Inhibitors of Amyloid Aggregation

RAMAZZOTTI, MATTEO;PAOLI, PAOLO;VIGLIANISI, CATERINA;MENICHETTI, STEFANO;DEGL'INNOCENTI, DONATELLA
2017

Abstract

The study of compounds able to interfere in various ways with amyloid aggregation is of paramount importance in amyloid research. Molecules characterized by a 4-thiaflavane skeleton have received great attention in chemical, medicinal, and pharmaceutical research. Such molecules, especially polyhydroxylated 4-thiaflavanes, can be considered as structural mimickers of several natural polyphenols that have been previously demonstrated to bind and impair amyloid fibril formation. In this work, we tested five different 4-thiaflavanes on the hen egg-white lysozyme (HEWL) amyloid model for their potential anti-amyloid properties. By combining a thioflavin T assay, atomic force microscopy, and a cell toxicity assay, we demonstrated that such compounds can impair the formation of high-order amyloid aggregates and mature fibrils. Despite this, the tested 4-thiaflavanes, although non-toxic per se, are not able to prevent amyloid toxicity on human neuroblastoma cells. Rather, they proved to block early aggregates in a stable, toxic conformation. Accordingly, 4-thiaflavanes can be proposed for further studies aimed at identifying blocking agents for the study of toxicity mechanisms of amyloid aggregation.
2
6
17
Ramazzotti, Matteo; Paoli, Paolo; Tiribilli, Bruno; Viglianisi, Caterina; Menichetti, Stefano; Degl’Innocenti, Donatella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1080836
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