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Issue 32, 2012
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Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells

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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.

Graphical abstract: Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells

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Publication details

The article was received on 01 May 2012, accepted on 21 Jun 2012 and first published on 21 Jun 2012


Article type: Paper
DOI: 10.1039/C2OB25830G
Org. Biomol. Chem., 2012,10, 6537-6546
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    Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells

    S. Müller, D. A. Sanders, M. Di Antonio, S. Matsis, J. Riou, R. Rodriguez and S. Balasubramanian, Org. Biomol. Chem., 2012, 10, 6537
    DOI: 10.1039/C2OB25830G

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