ARCA è l'archivio istituzionale ad accesso aperto della ricerca dell'Università Ca' Foscari Venezia e nasce nel 2014 con lo scopo di raccogliere, diffondere e conservare la produzione scientifica dell'Università. Costituisce di fatto il catalogo della ricerca di Ateneo.ARCA è un sistema Open Access: è non solo consultabile da tutti e visibile nei motori di ricerca, ma anche interoperabile con il portale cerCa. In questo modo vengono valorizzate la produzione scientifica dell'Ateneo e la visibilità dei ricercatori.
EnglishThe 3,30,5,50-tetrachloro-2-iodo-4,40-bipyridine structure is proposed as a novel chemical scaold for the design of new transthyretin (TTR) fibrillogenesis inhibitors. In the frame of a proof-of-principle exploration, four chiral 3,30,5,50-tetrachloro-2-iodo-20-substituted-4,40- bipyridines were rationally designed and prepared from a simple trihalopyridine in three steps, including a Cu-catalysed Finkelstein reaction to introduce iodine atoms on the heteroaromatic scaold, and a Pd-catalysed coupling reaction to install the 20-substituent. The corresponding racemates, along with other five chiral 4,40-bipyridines containing halogens as substituents, were enantioseparated by high-performance liquid chromatography in order to obtain pure enantiomer pairs. All stereoisomers were tested against the amyloid fibril formation (FF) of wild type (WT)-TTR and two mutant variants, V30M and Y78F, in acid mediated aggregation experiments. Among the 4,40-bipyridine derivatives, interesting inhibition activity was obtained for both enantiomers of the 3,30,5,50-tetrachloro-20-(4-hydroxyphenyl)-2-iodo-4,40-bipyridine. In silico docking studies were carried out in order to explore possible binding modes of the 4,40-bipyridine derivatives into the TTR. The gained results point out the importance of the right combination of H-bond sites and the presence of iodine as halogen-bond donor. Both experimental and theoretical evidences pave the way for the utilization of the iodinated 4,40-bipyridine core as template to design new promising inhibitors of TTR amyloidogenesis.
| Autori: | Cossu, Sergio [Funding Acquisition] |
| Data di pubblicazione: | 2020 |
| Titolo: | Rational Design, Synthesis, Characterization and Evaluation of Iodinated 4,4′-Bipyridines as New Transthyretin Fibrillogenesis Inhibitors |
| Rivista: | MOLECULES |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/molecules25092213 |
| Volume: | 25 |
| Appare nelle tipologie: | 2.1 Articolo su rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2020 molecules-25-02213-v2.pdf | Articolo principale | Documento in Post-print |  | Open Access Visualizza/Apri |
http://hdl.handle.net/10278/3726078
Copyright © 2021