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Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex.

ABSTRACT: Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able to induce telomeric DNA damage that may explain the activity of these compounds.

SUBMITTER: Amato J

PROVIDER: S-EPMC4109613 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Bis-indole derivatives with antitumor activity turn out to be specific ligands of human telomeric G-quadruplex.

Amato Jussara J Iaccarino Nunzia N Pagano Bruno B Morigi Rita R Locatelli Alessandra A Leoni Alberto A Rambaldi Mirella M Zizza Pasquale P Biroccio Annamaria A Novellino Ettore E Randazzo Antonio A

Frontiers in chemistry 20140724

Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a particular affinity for the parallel form of the human telomeric G-quadruplex. Both compounds are also able ...[more]

PMID: 25105115

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