Antitumor Polycyclic Acridines. 20. Search for DNA Quadruplex Binding Selectivity in a Series of 8,13-Dimethylquino[4,3,2-kl]acridinium Salts: Telomere- Targeted Agents

• DOI: 10.1021/jm070587t
• Publication Date: 2008-02-02T06:00:27Z
• Authors: Mai-Kim Cheng; Chetna Modi; Jennifer C. Cookson; Ian Hutchinson; Robert A. Heald; Andrew J. McCarroll; Sotiris Missailidis; Farial Tanious; W. David Wilson; Jean-Louis Mergny; Charles A. Laughton; Malcolm F. G. Ste...
• Keywords: G-quadruplex; Binding selectivity

The growth-inhibitory activities of an extensive series quaternized quino[4,3,2-kl]acridinium salts against tumor cell lines in vitro have been measured and their biological properties interpreted the light differential binding to different DNA isoforms. Selectivity for quadruplex stabilization by compounds were explored through array methods: UV absorption fluorescence emission spectroscopy, surface plasmon resonance, competition dialysis. Quadruplex interaction was further characterized FRET polymerase arrest assays. Telomerase inhibition, inferred from TRAP assay, is attributed stabilization, supported strong correlation (R2 = 0.81) across between affinity inhibition potency. Growth potency NCI60 human line panel more marked with greater duplex 0.82). Quantification relative constants puts some these ligands among most selective interactive agents reported date.