@article{Perrone2015, abstract = {We have previously reported that stabilization of the G-quadruplex structures in the HIV-1 Long Terminal Repeat (LTR) promoter suppresses viral transcription. Here we sought to develop new G-quadruplex ligands to be exploited as antiviral compounds by enhancing binding towards the viral G-quadruplex structures. We synthesized naphthalene diimide derivatives with a lateral expansion of the aromatic core. The new compounds were able to bind/stabilize the G-quadruplex to a high extent and some of them displayed clear-cut selectivity towards the viral G-quadruplexes with respect to the human telomeric G-quadruplexes. This feature translated into low nanomolar anti-HIV-1 activity towards two viral strains and encouraging selectivity indexes. The selectivity depended on specific recognition of LTR loop residues; the mechanism of action was ascribed to inhibition of LTR promoter activity in cells. This is the first example of G-quadruplex ligands that show increased selectivity towards the viral G-quadruplexes and display remarkable antiviral activity.}, author = {Perrone, Rosalba and Doria, Filippo and Butovskaya, Elena and Frasson, Ilaria and Botti, Silvia and Scalabrin, Matteo and Lago, Sara and Grande, Vincenzo and Nadai, Matteo and Freccero, Mauro and Richter, Sara N.}, doi = {10.1021/acs.jmedchem.5b01283}, journal = {Journal of Medicinal Chemistry}, month = {nov}, pages = {9639-9652}, title = {Synthesis, Binding and Antiviral Properties of Potent Core-Extended Naphthalene Diimides Targeting the HIV-1 Long Terminal Repeat Promoter G-Quadruplexes}, url = {https://doi.org/10.1021/acs.jmedchem.5b01283}, volume = {58}, year = {2015} }