Promoting the formation and stabilization of human telomeric G-quadruplex DNA, inhibition of telomerase and cytotoxicity by phenanthroline derivatives.

Four new di-substituted phenanthroline-based compounds a-d have been designed and prepared, and they have been shown to induce the formation of anti-parallel structure of human telomeric G-quadruplex DNA by CD spectra. FRET assay indicates that the melting temperature increases (ΔT(m) values) of G-quadruplex in buffer (pH 7.4) containing 100 mM NaCl are 31.6, 34.6, 17.8 and 32.6 °C for the compounds (1.0 μM) a, b, c and d, respectively. Competitive FRET assay shows that the four compounds exhibit a high G-quadruplex DNA selectivity over duplex DNA. Three of the compounds are the potent telomerase inhibitors and HeLa cell proliferation inhibitors.