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.
|Titolo:||Design, synthesis, biophysical and biological studies of trisubstitutednaphthalimides as G-quadruplex ligands|
|Autori interni:||PEDUTO, ANTONELLA|
|Data di pubblicazione:||2011|
|Rivista:||BIOORGANIC & MEDICINAL CHEMISTRY|
|Appare nelle tipologie:||1.1.2 Articolo su rivista con ISSN|