A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex
ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)3 binding
was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex
with compounds showing the best affinity has been studied by isothermal titration calorimetry and UVmelting
experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a
2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase
by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human
lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell
proliferation was observed for all cellular lines during short-term treatment
