Design and synthesis of a new dimeric xanthone derivative: enhancement of G-quadruplex selectivity and telomere damage

Marco Franceschin (1) , Daniele Nocioni (1) , Annamaria Biroccio (2) , Emanuela Micheli (3, 4) , Stefano Cacchione (3, 4) , Chiara Cingolani (2) , Alessandro Venditti (1) , Pasquale Zizza (2) , Armandodoriano Bianco (1) , Alessandro Altieri (1)

1 Department of Biochemical Sciences
2 Experimental Chemotherapy Laboratory
3 Department of Biology and Biotechnology "Charles Darwin"
4 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti

Following the results we previously reported on a series of xanthene and xanthone derivatives as G-quad-ruplex stabilizing ligands, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand, specifically its aromatic extension. In particular, here we report the design, synthesis and activity data of a new compound obtained by dimerization of the xanthene core (HELIXA4C). The reported results show that extension of the aromatic core and the increase of the number of polar side chains led to a great enhancement of G-quadruplex selectivity and telomere damage capability, as derived using ESI-MS evaluation, in vitro cancer screening and specific immunofluorescence assays.

Domains: Biochemistry, Molecular Biology

Marco Franceschin, Daniele Nocioni, Annamaria Biroccio, Emanuela Micheli, Stefano Cacchione, et al.. Design and synthesis of a new dimeric xanthone derivative: enhancement of G-quadruplex selectivity and telomere damage. Organic & Biomolecular Chemistry, 2014, 12 (47), pp.9572-82. ⟨10.1039/c4ob01658k⟩. ⟨pasteur-01163662⟩