Authors:
S Müller, DA Sanders, M Di Antonio, S Matsis, J-F Riou, R Rodriguez, S Balasubramanian
Journal name: 
Org Biomol Chem
Citation info: 
10(32):6537-6546
Abstract: 
The synthesis, biophysical and biological evaluation of a series of G-quadruplex interacting small molecules based on a N,N'-bis(quinolinyl)pyridine-2,6-dicarboxamide scaffold is described. The synthetic analogues were evaluated for their ability to stabilize telomeric G-quadruplex DNA, some of which showed very high stabilization potential associated with high selectivity over double-stranded DNA. The compounds exhibited growth arrest of cancer cells with detectable selectivity over normal cells. Long-time growth arrest was accompanied by senescence, where telomeric dysfunction is a predominant mechanism together with the accumulation of restricted DNA damage sites in the genome. Our data emphasize the potential of a senescence-mediated anticancer therapy through the use of G-quadruplex targeting small molecules based on the molecular framework of pyridostatin.
DOI: 
http://doi.org/10.1039/c2ob25830g
Research group: 
Balasubramanian Group
E-pub date: 
28 Aug 2012