Nucleoside analogues represent an important class of drug candidates. With the aim of searching for novel bioactive nucleosides, we developed an efficient synthetic way to construct a series of aryl 1,2,3-triazole acyclic C-azanucleosides via Huisgen 1,3-dipolar cycloaddition. The aryl 1,2,3-triazole motifs within these azanucleosides showed coplanar features, suggesting they could act as surrogates for large planar aromatic systems or nucleobases. Moreover, several aryltriazole acyclic C-azanucleosides bearing long alkyl chains exhibited potent antiproliferative activity against various cancer cell lines via induction of apoptosis. Most interestingly, the lead compound significantly down-regulated the key proteins involved in the heat shock response pathway, representing the first anticancer acyclic azanucleoside with such a mode of action. These novel aryl 1,2,3-triazole cyclic C-azanucleosides therefore serve as promising paradigms for further exploring anticancer drug candidates.
Novel aryltriazole acyclic C-azanucleosides as anticancer candidates
Pricl, Sabrina;
2020-01-01
Abstract
Nucleoside analogues represent an important class of drug candidates. With the aim of searching for novel bioactive nucleosides, we developed an efficient synthetic way to construct a series of aryl 1,2,3-triazole acyclic C-azanucleosides via Huisgen 1,3-dipolar cycloaddition. The aryl 1,2,3-triazole motifs within these azanucleosides showed coplanar features, suggesting they could act as surrogates for large planar aromatic systems or nucleobases. Moreover, several aryltriazole acyclic C-azanucleosides bearing long alkyl chains exhibited potent antiproliferative activity against various cancer cell lines via induction of apoptosis. Most interestingly, the lead compound significantly down-regulated the key proteins involved in the heat shock response pathway, representing the first anticancer acyclic azanucleoside with such a mode of action. These novel aryl 1,2,3-triazole cyclic C-azanucleosides therefore serve as promising paradigms for further exploring anticancer drug candidates.File | Dimensione | Formato | |
---|---|---|---|
OBC_prereferaggio.pdf
Accesso chiuso
Descrizione: main paper
Tipologia:
Bozza finale post-referaggio (post-print)
Licenza:
Creative commons
Dimensione
892.95 kB
Formato
Adobe PDF
|
892.95 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
d0ob02164d.pdf
Accesso chiuso
Tipologia:
Documento in Versione Editoriale
Licenza:
Copyright Editore
Dimensione
1.94 MB
Formato
Adobe PDF
|
1.94 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
d0ob02164d1.pdf
Accesso chiuso
Descrizione: Supplementary material
Tipologia:
Altro materiale allegato
Licenza:
Copyright Editore
Dimensione
2.65 MB
Formato
Adobe PDF
|
2.65 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.