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

Journal of Medicinal Chemistry
2017.0

Abstract

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.

Knowledge Graph

Similar Paper

Lead Discovery of Dual G-Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases (PARPs) Inhibitors: A New Avenue in Anticancer Treatment
Journal of Medicinal Chemistry 2017.0
Discovery of Novel Schizocommunin Derivatives as Telomeric G-Quadruplex Ligands That Trigger Telomere Dysfunction and the Deoxyribonucleic Acid (DNA) Damage Response
Journal of Medicinal Chemistry 2018.0
Aminoacyl−Anthraquinone Conjugates as Telomerase Inhibitors: Synthesis, Biophysical and Biological Evaluation
Journal of Medicinal Chemistry 2008.0
N-Cyclic Bay-Substituted Perylene G-Quadruplex Ligands Have Selective Antiproliferative Effects on Cancer Cells and Induce Telomere Damage
Journal of Medicinal Chemistry 2011.0
Discovery of Quinazoline-2,4(1H,3H)-dione Derivatives Containing 3-Substituted Piperizines as Potent PARP-1/2 Inhibitors─Design, Synthesis, In Vivo Antitumor Activity, and X-ray Crystal Structure Analysis
Journal of Medicinal Chemistry 2021.0
Synthesis and Evaluation of Quindoline Derivatives as G-Quadruplex Inducing and Stabilizing Ligands and Potential Inhibitors of Telomerase
Journal of Medicinal Chemistry 2005.0
Tri-armed ligands of G-quadruplex on heteroarene-fused anthraquinone scaffolds: Design, synthesis and pre-screening of biological properties
European Journal of Medicinal Chemistry 2018.0
4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1
Journal of Medicinal Chemistry 2008.0
G-Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents
Journal of Medicinal Chemistry 2018.0
Shooting for Selective Druglike G-Quadruplex Binders: Evidence for Telomeric DNA Damage and Tumor Cell Death
Journal of Medicinal Chemistry 2012.0