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

Bis-indolinone derivatives having either2,6-disubstituted pyridine core(1a and1b) 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.