A series of bay-substituted perylene derivatives is reported as a new class of G-quadruplex ligands. The synthesized compounds hive differing N-cyclic substituents on the bay area and differing side chains on the perylene major axis. ESI-MS and FEET measurements highlighted the strongest quadruplex binders in this series and those showing the highest quadruplex/duplex selectivity. Several biological assays were performed on these compounds, which showed that compound 5 (PPL3C) triggered a DNA damage response in transformed cells with the formation of telomeric foci containing phosphorylated gamma-H2AX and 53BP1. This effect mainly occurred in replicating cells and was consistent with Pod dissociation. Compound S does not induce telomere damage in normal cells, which are unaffected by treatment with the: compound, suggesting that this agent preferentially kills cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs.

N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage / Casagrande, Valentina; Erica, Salvati; Alvino, Antonello; Bianco, Armandodoriano; Alina, Ciammaichella; C., Dangelo; GINNARI SATRIANI, Luca; Serrilli, ANNA MARIA; Iachettini, Sara; Carlo, Leonetti; Stephen, Neidle; Ortaggi, Giancarlo; Manuela, Porru; Angela, Rizzo; Marco, Franceschin; Annamaria, Biroccio. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 54:5(2011), pp. 1140-1156. [10.1021/jm1013665]

N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage

CASAGRANDE, VALENTINA;ALVINO, Antonello;BIANCO, Armandodoriano;GINNARI SATRIANI, LUCA;SERRILLI, ANNA MARIA;IACHETTINI, SARA;ORTAGGI, Giancarlo;
2011

Abstract

A series of bay-substituted perylene derivatives is reported as a new class of G-quadruplex ligands. The synthesized compounds hive differing N-cyclic substituents on the bay area and differing side chains on the perylene major axis. ESI-MS and FEET measurements highlighted the strongest quadruplex binders in this series and those showing the highest quadruplex/duplex selectivity. Several biological assays were performed on these compounds, which showed that compound 5 (PPL3C) triggered a DNA damage response in transformed cells with the formation of telomeric foci containing phosphorylated gamma-H2AX and 53BP1. This effect mainly occurred in replicating cells and was consistent with Pod dissociation. Compound S does not induce telomere damage in normal cells, which are unaffected by treatment with the: compound, suggesting that this agent preferentially kills cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs.
01 Pubblicazione su rivista::01a Articolo in rivista
N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage / Casagrande, Valentina; Erica, Salvati; Alvino, Antonello; Bianco, Armandodoriano; Alina, Ciammaichella; C., Dangelo; GINNARI SATRIANI, Luca; Serrilli, ANNA MARIA; Iachettini, Sara; Carlo, Leonetti; Stephen, Neidle; Ortaggi, Giancarlo; Manuela, Porru; Angela, Rizzo; Marco, Franceschin; Annamaria, Biroccio. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 54:5(2011), pp. 1140-1156. [10.1021/jm1013665]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/341173
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 49
  • ???jsp.display-item.citation.isi??? 47
social impact