RT info:eu-repo/semantics/article T1 PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex A1 Gratal Viñuales, Patricia Betsabe A1 González Quero, Julia A1 Pérez Redondo, Adrián A1 Gándara Barreiro, Zoila A1 Gude Rodríguez, Lourdes K1 1,10-phenanthroline K1 guanyl hydrazones K1 human telomeric quadruplex K1 DNA interactions K1 antitumor agents K1 Química K1 Chemistry AB A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a twostep procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA.DNA interactions with polymorphic G-quadruplex telomeric structures were studied by differenttechniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circulardichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficientlyrecognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinityand quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activityagainst a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity isconsiderably lower in healthy human cells (HFF-1 and RPWE-1). SN 1422-0067 YR 2021 FD 2021-01-13 LK http://hdl.handle.net/10017/45847 UL http://hdl.handle.net/10017/45847 LA eng DS MINDS@UW RD 28-mar-2024