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Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone...

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Detalles Bibliográficos
Autores principales: Altieri, Alessandro, Alvino, Antonello, Ohnmacht, Stephan, Ortaggi, Giancarlo, Neidle, Stephen, Nocioni, Daniele, Franceschin, Marco, Bianco, Armandodoriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269716/
https://www.ncbi.nlm.nih.gov/pubmed/24177701
http://dx.doi.org/10.3390/molecules181113446
Descripción
Sumario:Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data.