Shooting for Selective Druglike G-Quadruplex Binders: Evidence for Telomeric DNA Damage and Tumor Cell Death

作者：Cosconati Sandro; Rizzo Angela; Trotta Roberta; Pagano Bruno; Iachettini Sara; De Tito Stefano; Lauri Ilaria; Fotticchia Iolanda; Giustiniano Mariateresa; Marinelli Luciana; Giancola Concetta; Novellino Ettore; Biroccio Annamaria^*; Randazzo Antonio

来源：Journal of Medicinal Chemistry, 2012, 55(22): 9785-9792.

DOI：10.1021/jm301019w

Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring end-stacking binding properties. Against this general trend, we were persuaded that the G-quadruplex grooves can recognize molecular entities with better drug-like and selectivity properties. From this idea, a, set of small molecules was identified and the structural features responsible for G-quadruplex recognition were delineated. These compounds were demonstrated to have enhanced affinity and selectivity for the G-quadruplex over the duplex structure. Their ability to induce selective DNA damage at telomeric level and to induction of apoptosis and Senescence on tumor, cells, is herein experimentally proven.

• 出版日期2012-11-22