Casagrande, V., Salvati, E., Alvino, A., Bianco, A., Ciammaichella, A., D'Angelo, C., Ginnari-Satriani, L., Serrilli, A.M., Iachettini, S., Leonetti, C., Neidle, S., Ortaggi, G., Porru, M., Rizzo, A., Franceschin, M. and Biroccio, A. (2011) N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage. Journal of Medicinal Chemistry . 10.1021/jm1013665 .
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A series of bay-substituted perylene derivatives is reported as a new class of G-quadruplex ligands. The synthesized compounds have differing N-cyclic substituents on the bay area and differing side chains on the perylene major axis. ESI-MS and FRET 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 γ-H2AX and 53BP1. This effect mainly occurred in replicating cells and was consistent with Pot1 dissociation. Compound 5 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.
|Departments, units and centres:||Department of Pharmaceutical and Biological Chemistry > Centre for Pharmacognosy and Phytotherapy|
|Journal or Publication Title:||Journal of Medicinal Chemistry|
|Deposited By:||Library Staff|
|Deposited On:||24 Feb 2011 17:56|
|Last Modified:||13 May 2011 08:56|
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