Synthesis and Activity Evaluation of 9-O-Substituted Berberine Derivatives Containing Polyamine Chain as Highly Selective Telomeric G-Quadruplex Stabilizing Ligands

A series of 9-O-substituted berberine derivatives (5a-5c) as telomeric quadruplex ligands was synthesized and evaluated. The interaction of berberine derivatives with telomeric G-quadruplex DNA was examined by CD spectroscopy, FRET-melting method, fluorescence titration assay and PCR-stop assay. The CD results indicated the derivatives were capable of inducing the formation of antiparallel G-quadruplex and the results from FRET-melting method clearly showed that derivatives with polyamine chain had high binding affinity and superior selectivity for telomeric G-quadruplex DNA over duplex. The PCR-stop assay results exhibited the inhibitory effect on the hybridization. All the results suggested the 9-O-substituted berberine derivatives were highly selective telomeric G-quadruplex DNA stabilizing ligands.