Lead Discovery of Dual G‑Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases (PARPs) Inhibitors: A New Avenue in Anticancer Treatment

G-quadruplex stabilizers
are an established opportunity in anticancer
chemotherapy. To circumvent the antiproliferative effects of G4 ligands,
cancer cells recruit PARP enzymes at telomeres. Herein, starting from
the structural similarity of a potent G4 ligand previously discovered
by our group and a congeneric PARP inhibitor, a library of derivatives
was synthesized to discover the first dual G4/PARP ligand. We demonstrate
that a properly decorated thieno­[3,2-c]­quinolin-4­(5H)-one stabilizes the G4 fold in vitro and in cells, induces a DNA damage response localized to telomeres,
inhibits PARylation in cells, and has an antiproliferative effect
in BRCA2 deficient tumor cells.